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題 名 | Characterization of Mouse Cytochrome P450-catalyzed Oxidative Metabolism of Rutaecarpine, an Alkaloid in the Herbal Medicine Evodia Rutaecarpa=鼷鼠細胞色素P450催化之吳茱萸生物鹼Rutaecarpine氧化代謝作用的探討 |
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作 者 | 詹婉卿; 董明兆; 何禮剛; 陳介甫; 翁芸芳; | 書刊名 | 藥物食品分析 |
卷 期 | 14:2 2006.06[民95.06] |
頁 次 | 頁159-165+220 |
分類號 | 414.51 |
關鍵詞 | Rutaecarpine羥化作用; 細胞色素P450; 鼷鼠; 肝; Rutaecarpine hydroxylation; Cytochrome P450; Mice; Liver; |
語 文 | 英文(English) |
中文摘要 | 吳茱英生物鹼rutaecarpine具有抗血栓與血管舒張作用,為分析鼷鼠細胞色素tP450 (P450,CYP) 所催化之rutaecarpme羥化作用,使用肝微粒體探討rutaecarpine羥化作用之誘導、抑制、動力學性質。在未處理之鼷鼠,rutaecarpine10-,11-,12-,3-羥化活性之Km與Vmax值分別為11.6-16.7μM與62-197pmol/min/mg protein。Rutaecarpine羥化活性受αnaphthoflavone與orphenadrine抑制,但不受sulfaphenazole與ketoconazole影響。3-methylcholanthrene處理增加rutaecarpine 10-、11-、12-、3-羥化活性。phenobarbital處理增加rutaecarpine 10-、11-、12-、3-羥化活性。相反地,dexamethasone對這些羥化活性均無影響。這些結果顯示CYP1A與CYP2B在鼷鼠肝rutaecarpine羥化作用中扮演重要角色。但CYP3A不是主要參與此代謝作用之主要P450。 |
英文摘要 | The alkaloid rutaecarpine exhibits antithrombotic and vasorelaxant effects. To characterize mouse cytochrome P450 (P450, CYP)-catalyzed rutaecarpine hydroxylations, the induction, inhibition, and kinetic properties of rutaecarpine hydroxylations were determined using liver microsomes of C57BL/6J mice. In untreated mice, rutaecarpine 10-, 11-, 12-, and 3-hydroxylation had Km and Vmax values ranging, respectively, between 11.6~16.7 μM and 62~197 pmol/min/mg protein. The formation rates of the four hydroxylated metabolites were inhibited by α-naphthoflavone and orphenadrine, but not by either sulfaphenazole or ketoconazole. 3-Methylcholanthrene-treatment increased rutaecarpine 11-, 12-, and 3-hydroxylation activities. Phenobarbital-treatment increased rutaecarpine 10-, 11-, 12-, and 3-hydroxylation activities. Dexamethasone had no effect on these hydroxylation reactions in mice. These results indicated that CYP1A and CYP2B, but not CYP3A, play major roles in rutaecarpine hydroxylations in mice. Abbreviations: CYP, cytochrome P450; 3-MC, 3-methylcholanthrene; G6P, glucose-6-phosphate; α-NF, α-naphthoflavone; β-NADP+, β-nicotinamide adenine dinucleotide phosphate. |
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