In vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomes.
Biopharm Drug Dispos
; 34(4): 195-202, 2013 May.
Article
en En
| MEDLINE
| ID: mdl-23446989
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Éteres Fenílicos
/
Microsomas Hepáticos
/
Sistema Enzimático del Citocromo P-450
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biopharm Drug Dispos
Año:
2013
Tipo del documento:
Article