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The time-dependent effects of St John's wort on cytochrome P450, uridine diphosphate-glucuronosyltransferase, glutathione S-transferase, and NAD(P)H-quinone oxidoreductase in mice.
Yang, Jin-Fu; Liu, Yue-Rong; Huang, Chiung-Chiao; Ueng, Yune-Fang.
Afiliação
  • Yang JF; National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC.
  • Liu YR; Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
  • Huang CC; National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC.
  • Ueng YF; National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC.
J Food Drug Anal ; 26(1): 422-431, 2018 01.
Article em En | MEDLINE | ID: mdl-29389584
Hypericum perforatum [St. John's wort (SJW)] is known to cause a drug interaction with the substrates of cytochrome P450 (P450, CYP) isoforms, mainly CYP3A. This study aims to determine the dose response and time course of the effects of SJW extract on P450s, UDP-glucuronosyltransferase (UGT), glutathione S-transferase (GST), and NAD(P)H-quinone oxidoreductase (NQO) in mice. The oral administration of SJW extract to male mice at 0.6 g/kg/d for 21 days increased hepatic oxidation activity toward a Cyp3a substrate nifedipine. By extending the SJW treatment to 28 days, hepatic nifedipine oxidation (NFO) and warfarin 7-hydroxylation (WOH) (Cyp2c) activities were increased by 95% and 34%, respectively. Immunoblot analysis of liver microsomal proteins revealed that the Cyp2c protein level was elevated by the 28-day treatment. However, the liver microsomal activities of the oxidation of the respective substrates of Cyp1a, Cyp2a, Cyp2b, Cyp2d, and Cyp2e1 remained unchanged. In the kidney, SJW increased the NFO, but not the WOH activity. The extended 28-day treatment did not alter mouse hepatic and renal UGT, GST, and NQO activities. These findings demonstrate that SJW stimulates hepatic and renal Cyp3a activity and hepatic Cyp2c activity and expression. The induction of hepatic Cyp2c requires repeated treatment for a period longer than the initial induction of Cyp3a.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Extratos Vegetais / NAD(P)H Desidrogenase (Quinona) / Glucuronosiltransferase / Hypericum / Sistema Enzimático do Citocromo P-450 / Glutationa Transferase / NAD Limite: Animals Idioma: En Revista: J Food Drug Anal Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Extratos Vegetais / NAD(P)H Desidrogenase (Quinona) / Glucuronosiltransferase / Hypericum / Sistema Enzimático do Citocromo P-450 / Glutationa Transferase / NAD Limite: Animals Idioma: En Revista: J Food Drug Anal Ano de publicação: 2018 Tipo de documento: Article