Inhibitory effects of deoxypodophyllotoxin from Anthriscus sylvestris on human CYP2C9 and CYP3A4.
Planta Med
; 76(7): 701-4, 2010 May.
Article
en En
| MEDLINE
| ID: mdl-19960413
ABSTRACT
Deoxypodophyllotoxin (DPT) is a bioactive compound of Anthriscus sylvestris (Apiaceae). In the present study, the inhibition of cytochrome P450 (CYP) by DPT was evaluated in human liver microsomes (HLM) and the baculovirus-insect cell-expressed human CYPs using a cocktail probe assay. When a mixture of specific CYP substrates was incubated with DPT in HLM, CYP2C9-catalyzed diclofenac 4-hydroxylation and CYP3A4-catalyzed midazolam 1-hydroxylation were strongly inhibited by DPT, with IC (50) values of 6.3 and 9.2 microM, respectively. The Lineweaver-Burke plots for the inhibition of CYP2C9 and CYP3A4 in HLM and baculovirus-insect cell-expressed human CYPs were consistent with a competitive type of inhibition. From these results, DPT was characterized to be a competitive inhibitor of CYP2C9 and CYP3A4, with K(i) values of 3.5 and 10.8 microM in HLM and 24.9 and 3.5 microM in baculovirus-insect cell-expressed human CYPs, respectively.
Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Podofilotoxina
/
Hidrocarburo de Aril Hidroxilasas
/
Apiaceae
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Inhibidores del Citocromo P-450 CYP3A
Límite:
Humans
Idioma:
En
Revista:
Planta Med
Año:
2010
Tipo del documento:
Article