Andrographis paniculata Extract and Andrographolide Modulate the Hepatic Drug Metabolism System and Plasma Tolbutamide Concentrations in Rats

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题名:	Andrographis paniculata Extract and Andrographolide Modulate the Hepatic Drug Metabolism System and Plasma Tolbutamide Concentrations in Rats
作者:	Chen, HW;Chen, HW;黃晉修;Huang, Chin-Shiu;Liu, PF;Liu, PF;Li, CC;Li, CC;Chen, CT;Chen, CT;Liu, CT;Liu, CT;Chiang, JR;Chiang, JR;Yao, HT;Yao, HT;李宗貴;Lii, Chong-Kuei
贡献者:	保健營養生技學系
关键词:	CONSTITUTIVE ANDROSTANE RECEPTOR;GLUTATHIONE-S-TRANSFERASE;MESSENGER-RNA EXPRESSION;PREGNANE X RECEPTOR;PHASE-II ENZYMES;ACTIVE DITERPENOIDS;SIGNALING PATHWAY;LIVER-MICROSOMES;DIABETIC-RATS;IN-VITRO
日期:	201308
上传时间:	2013-10-29 09:37:32 (UTC+0)
摘要:	Andrographolide is the most abundant terpenoid of A. paniculata which is used in the treatment of diabetes. In this study, we investigated the effects of A. paniculata extract (APE) and andrographolide on the expression of drug-metabolizing enzymes in rat liver and determined whether modulation of these enzymes changed the pharmacokinetics of tolbutamide. Rats were intragastrically dosed with 2 g/kg/day APE or 50 mg/kg/day andrographolide for 5 days before a dose of 20 mg/kg tolbutamide was given. APE and andrographolide reduced the AUC0-12 h of tolbutamide by 37% and 18%, respectively, compared with that in controls. The protein and mRNA levels and enzyme activities of CYP2C6/11, CYP1A1/2, and CYP3A1/2 were increased by APE and andrographolide. To evaluate whether APE or andrographolide affected the hypoglycemic action of tolbutamide, high-fat diet-induced obese mice were used and treated in the same manner as the rats. APE and andrographolide increased CYP2C6/11 expression and decreased plasma tolbutamide levels. In a glucose tolerance test, however, the hypoglycemic effect of tolbutamide was not changed by APE or andrographolide. These results suggest that APE and andrographolide accelerate the metabolism rate of tolbutamide through increased expression and activity of drug-metabolizing enzymes. APE and andrographolide, however, do not impair the hypoglycemic effect of tolbutamide.
關聯:	Evidence-based Complementary and Alternative Medicine, 2013:982689.
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