篇名 | Characterization of Mouse Cytochrome P450-catalyzed Oxidative Metabolism of Rutaecarpine, an Alkaloid in the Herbal Medicine Evodia rutaecarpa |
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卷期 | 14:2 |
作者 | WOAN-CHING JAN 、 MING-JAW DON 、 LI-KANG HO 、 CHIEH-FU CHEN 、 YUNE-FANG UENG |
頁次 | 159-165 |
關鍵字 | rutaecarpine hydroxylation 、 cytochrome P450 、 mice 、 liver 、 MEDLINE 、 Scopus 、 SCIE |
出刊日期 | 200606 |
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.