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Effect of Gegen Qinlian decoction on hepatic cytochrome CYP450 isozymes in rats by HPLC-MS/MS / 中国中药杂志
China Journal of Chinese Materia Medica ; (24): 3072-3080, 2015.
Artigo em Chinês | WPRIM | ID: wpr-284796
ABSTRACT
To study the effect of Gegen Qinlian decoction and its major effective components on five hepatic microsomal CYP450 isozymes in rats. The in vitro hepatic microsomal incubation technique was used to co-culture Gegen Qinlian decoction and its major effective components together with each probe substrate. HPLC-MS/MS was used to establish the analytical method for metabolites of the five isoform probe substrates of CYP450 isozymes, detect the linearity among micoromal protein concentration, incubation time and metabolite formation amount. And HPLC-MS/MS was applied to determine the formation rate (V) of corresponding metabolites (acetaminophen, 4-OH-chlorzoxazone, dextrophan, 6-OH-chlorzoxazone and 6β-hydroxytestosterone) specific probe substrates of the five isoform probe substrates of CYP450 isozymes (phenacetin, polbutamide, dextromethorphan, chlorzoxazone, testosterone), in order to determine the activity of each isozyme. The result showed good linearity among acetaminophen, 4-OH-tolbutamide, dextrophan, 6-OH-chlorzoxazone and 6β-hydroxytestosterone, satisfactory precision, stability and average recovery, suggesting the method was feasible. The optimized in vitro microsomal incubation conditions conformed to the requirements in the guideline of drug-drug interaction. Gegen Qinlian decoction showed different degrees of inhibitor effect on 5 CYP450 isoforms (CYP1A2, CYP2C11, CYP2D2, CYP2E1, CYP3A1/2). Its major effective component berberine could inhibit each CYP450 isoform at high concentrations (except for CYP1A2, CYP3A1/2).
Assuntos
Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Farmacologia / Medicamentos de Ervas Chinesas / Cromatografia Líquida de Alta Pressão / Espectrometria de Massas em Tandem / Inibidores das Enzimas do Citocromo P-450 / Isoenzimas / Fígado / Métodos Limite: Animais Idioma: Chinês Revista: China Journal of Chinese Materia Medica Ano de publicação: 2015 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Farmacologia / Medicamentos de Ervas Chinesas / Cromatografia Líquida de Alta Pressão / Espectrometria de Massas em Tandem / Inibidores das Enzimas do Citocromo P-450 / Isoenzimas / Fígado / Métodos Limite: Animais Idioma: Chinês Revista: China Journal of Chinese Materia Medica Ano de publicação: 2015 Tipo de documento: Artigo