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P450 enzymes-based metabolic interactions between monarch drugs and the other constituent herbs: A strategy to explore compatibility mechanism of Sangju-Yin.
Phytomedicine ; 58: 152866, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30831464
ABSTRACT

BACKGROUND:

Herbal compatibility of compound formulas can enhance therapeutic effects or reduce side effects of the monarch drugs, but majority of compatibility mechanisms are still unknown. Sangju-Yin, a well-known Chinese compound formula, is currently used to treat common cold in clinical.

PURPOSE:

In this study, we proposed a strategy to explore the compatibility mechanism of Sangju-Yin by investigating P450 enzymes-based metabolic interactions between monarch drugs and the other constituent herbs.

METHODS:

Under the guidance of traditional Chinese medicine theory, the constituent herbs of Sangju-Yin were divided into four groups, including monarch drugs, monarch drugs with addition of minister drugs, monarch drugs with addition of minister and adjuvant drugs, as well as the whole recipe, namely monarch drugs with addition of minister, adjuvant and conductant drugs. Their effects on rats in vivo P450 (CYP1A2, CYP2A3, CYP2C6, CYP2C11 and CYP3A1) activities after oral administration were evaluated using probe drug assay based on LC-MS/MS. Moreover, effects of the four groups of herbs on mRNA expression of P450 enzymes after oral administration, as well as in vitro P450 activities after co-incubation, were investigated to explore the underlying mechanisms.

RESULTS:

Comparing with monarch drugs, addition of different constituent herbs significantly enhanced CYP1A2 and CYP2C6 activities, and inhibited CYP2A3 and CYP3A1 activities, indicating their possible influences on plasma concentrations of active constituents in the monarch drugs. Mechanism study suggested that these herbs affected P450 activities by transcriptional regulation and/or direct interaction with the enzymes.

CONCLUSION:

This study clarified the compatibility mechanism of Sangju-Yin from the aspect of P450 enzymes-based metabolic interactions, which would benefit better understanding of the therapeutic basis of Sangju-Yin.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Medicamentos de Ervas Chinesas / Sistema Enzimático do Citocromo P-450 / Composição de Medicamentos / Interações de Medicamentos / Medicina Tradicional Chinesa Limite: Animais Idioma: Inglês Revista: Phytomedicine Assunto da revista: Terapias Complementares Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: China