College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
Biopharm Drug Dispos. 2013 May;34(4):195-202. doi: 10.1002/bdd.1837. Epub 2013 Mar 26.
Obovatol, a major constituent of the leaves of Magnolia obovata Thunb, is known to inhibit nuclear factor-κB activity and arachidonic acid-induced platelet aggregation. This study was performed to identify the metabolites of obovatol in human liver microsomes. Human liver microsomes incubated with obovatol in the presence of NADPH and/or UDPGA resulted in the formation of six metabolites, M1-M6. M1 and M2 were identified as hydroxyobovatol, on the basis of liquid chromatography/tandem mass spectrometric (LC-MS/MS) analysis. M1, M2 and obovatol were further metabolized to their glucuronide conjugates, obovatol-glucuronide (M3), obovatol-diglucuronide (M4) and hydroxyobovatol-glucuronide (M5 and M6). The inhibitory potency of obovatol on eight major human P450s was also investigated in human liver microsomes. In these experiments, obovatol strongly inhibited CYP2C19-mediated S-mephenytoin hydroxylase activity with an IC(50) value of 0.8 µM, which could have implications for drug-drug interactions.
八角枫叶中的主要成分之一八角枫醇已知能够抑制核因子-κB 活性和花生四烯酸诱导的血小板聚集。本研究旨在鉴定人肝微粒体中八角枫醇的代谢物。在存在 NADPH 和/或 UDPGA 的情况下，用人肝微粒体孵育八角枫醇，导致形成六种代谢物 M1-M6。基于液相色谱/串联质谱分析（LC-MS/MS），鉴定 M1 和 M2 为羟基八角枫醇。M1、M2 和八角枫醇进一步代谢为它们的葡萄糖醛酸缀合物，即八角枫醇葡萄糖醛酸（M3）、八角枫醇二葡萄糖醛酸（M4）和羟基八角枫醇葡萄糖醛酸（M5 和 M6）。还在人肝微粒体中研究了八角枫醇对 8 种主要人 P450 的抑制作用。在这些实验中，八角枫醇强烈抑制 CYP2C19 介导的 S-美芬妥因羟化酶活性，IC50 值为 0.8 μM，这可能对药物相互作用有影响。
