The First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China.
Phytother Res. 2013 May;27(5):705-12. doi: 10.1002/ptr.4766. Epub 2012 Jul 5.
Evodiamine is the main active alkaloid of Evodia rutaecarpa (E. rutaecarpa) and has been demonstrated to exhibit many pharmacological activities including vasorelaxation, uterotonic action, anoxia and control of body temperature. The present study focused on the metabolism of evodiamine. Human and phenobarbital-induced rat liver microsomal incubation of evodiamine in the presence of NADPH resulted in the formation of five major metabolites (M-1, M-2, M-3, M-4, M-5). Four metabolites (M-1, M-2, M-3 and M-5) were identified to mono-hydroxylated evodiamine and one metabolite (M-4) was identified to be N-demethylated evodiamine. CYP3A4, CYP2C9 and CYP1A2 were identified to be the main CYP isoforms involved in the metabolism of evodiamine in human liver microsomes. Finding new metabolites can help us decipher novel substance basis of efficiency and toxicity. Elucidation of drug metabolizing enzymes will facilitate explaining the individual difference for response to the same drugs or herbs and the potential drug-drug interaction or herb-drug interaction. Taken together, these results are of significance for better understanding the pharmacokinetic behaviour of evodiamine and helpful for clinical application of evodiamine and E. rutaecarpa.
吴茱萸碱是吴茱萸（Evodia rutaecarpa）的主要活性生物碱，已被证明具有多种药理活性，包括血管舒张、子宫收缩作用、缺氧和体温控制。本研究集中于吴茱萸碱的代谢。在存在 NADPH 的情况下，用人肝微粒体和苯巴比妥诱导的大鼠肝微粒体孵育吴茱萸碱，导致形成五种主要代谢物（M-1、M-2、M-3、M-4、M-5）。鉴定出四种代谢物（M-1、M-2、M-3 和 M-5）为吴茱萸碱的单羟基化代谢物，一种代谢物（M-4）为吴茱萸碱的 N-去甲基化代谢物。鉴定出 CYP3A4、CYP2C9 和 CYP1A2 为参与人肝微粒体中吴茱萸碱代谢的主要 CYP 同工酶。发现新的代谢物有助于我们破译其疗效和毒性的新物质基础。阐明药物代谢酶将有助于解释对同一药物或草药的个体差异以及潜在的药物相互作用或草药-药物相互作用。综上所述，这些结果对于更好地理解吴茱萸碱的药代动力学行为具有重要意义，并有助于吴茱萸碱和吴茱萸的临床应用。
