title: In vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomes.
abstract: 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.
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors: Jeongmin
authors: J
authors: Joo
authors: Doohyun
authors: D
authors: Lee
authors: Zhexue
authors: Z
authors: Wu
authors: Jung-Hoon
authors: JH
authors: Shin
authors: Hye Suk
authors: HS
authors: Lee
authors: Byoung-Mog
authors: BM
authors: Kwon
authors: Tae-Lin
authors: TL
authors: Huh
authors: Yang-Weon
authors: YW
authors: Kim
authors: Su-Jun
authors: SJ
authors: Lee
authors: Tae Wan
authors: TW
authors: Kim
authors: Taeho
authors: T
authors: Lee
authors: Kwang-Hyeon
authors: KH
authors: Liu
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002853:Chromatography, Liquid; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D031566:Magnolia / Q000737:chemistry; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D010647:Phenyl Ethers / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism
chemical_list: D010647:Phenyl Ethers; D014535:Uridine Diphosphate Glucuronic Acid; D009249:NADP; C036796:obovatal; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19