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A methanol extract of each herbal medicine was prepared and then preincubated with human liver microsomes in the presence of an NADPH-generating system. Residual microsomal CYP3A4 and CYP2D6 activity was then determined by measuring the N-demethylation of erythromycin and the O-demethylation of dextromethorphan, respectively. Of the 26 herbal medicines tested, 16 were found to decrease the residual CYP3A4 activity in a preincubation time-dependent manner. The extract of Evodia Fruit caused the most dramatic decrease in residual CYP3A4 activity (i.e.22.3% residual activity after 30 min preincubation). A substantial decrease in residual CYP3A4 activity was also observed from extracts of Sappan Wood, Incised Notopterygium Rhizome, Schisandra Fruit, Great Burdock Achene, Angelica Dahurica Root and Rhubarb (residual activity of 40.6, 41.2, 53.4, 47.1, 53.4 and 59.2% after 30 min preincubation, respectively). 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Metabolism-dependent inhibition of CYP3A4 and CYP2D6 by extracts from 26 herbal medicines
http://hdl.handle.net/10110/1357
http://hdl.handle.net/10110/13572237dd2e-74e8-4993-a49f-6fd536c13768
名前 / ファイル | ライセンス | アクション |
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wakan04-iwata.pdf (514.8 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2007-12-13 | |||||
タイトル | ||||||
タイトル | Metabolism-dependent inhibition of CYP3A4 and CYP2D6 by extracts from 26 herbal medicines | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | herb | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | human liver microsomes | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | inhibition | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | CYP3A4 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | CYP2D6 | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Iwata, Hiroshi
× Iwata, Hiroshi× Tezuka, Yasuhiro× Kadota, Shigetoshi× Hiratsuka, Akira× Watabe, Tadashi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | A total of 26 herbal medicines were examined for their inhibitory effects on cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6). A methanol extract of each herbal medicine was prepared and then preincubated with human liver microsomes in the presence of an NADPH-generating system. Residual microsomal CYP3A4 and CYP2D6 activity was then determined by measuring the N-demethylation of erythromycin and the O-demethylation of dextromethorphan, respectively. Of the 26 herbal medicines tested, 16 were found to decrease the residual CYP3A4 activity in a preincubation time-dependent manner. The extract of Evodia Fruit caused the most dramatic decrease in residual CYP3A4 activity (i.e.22.3% residual activity after 30 min preincubation). A substantial decrease in residual CYP3A4 activity was also observed from extracts of Sappan Wood, Incised Notopterygium Rhizome, Schisandra Fruit, Great Burdock Achene, Angelica Dahurica Root and Rhubarb (residual activity of 40.6, 41.2, 53.4, 47.1, 53.4 and 59.2% after 30 min preincubation, respectively). These results are comparable to those using troleandomycin, a known irreversible inhibitor of CYP3A4, which gave a residual activity of 49.4% under identical conditions. 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。 |
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内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | relation: isVersionOf: http://ci.nii.ac.jp/naid/10014223212/ | |||||
書誌情報 |
Journal of traditional medicines 巻 21, 号 6, p. 281-286, 発行日 2004-12 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 18801447 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA12035198 | |||||
フォーマット | ||||||
内容記述タイプ | Other | |||||
内容記述 | application/pdf | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
スポンサー | ||||||
内容記述タイプ | Other | |||||
内容記述 | 21st Century COE Program Toyama Medical and Pharmaceutical University | |||||
出版者 | ||||||
出版者 | Medical and Pharmaceutical Society for WAKAN-YAKU = 和漢医薬学会 | |||||
資源タイプ(DSpace) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Article |