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Effects of Ziziphus jujuba fruit extracts on cytochrome P450(CYP1A2) activity in rats

Chinese Journal of Natural Medicines 2015年第8期13卷 588-594页

作者： JING Xin-Yue PENG Yun-Ru WANG Xin-Min DUAN Jin-Ao Laboratory of Integrated Acupuncture and Medicine Nanjing University of Chinese Medicine Jiangsu Provincial Institute of Traditional Chinese Medicine Jiangsu Key Laboratory for High Technology Research of TCM Formulae Nanjing University of Chinese Medicine

Drug-drug interactions have become a serious problem in the clinic, since plant-based medicines are extensively used. The present study investigated the effects of ziziphusjujuba fruit （Z J） extract on the pharmacokinetics of phenacetin, a typical substrate of a cytochrome P450 enzyme CYP 1A2, in rats. The rats were pretreated with the water extract （1.0 g·kg-l） or the ethanolic extract （3.6 g·kg-1） of ZJ for 10 days, and the pharmacokinetics of phenacetin was investigated after intravenous administration. In an in vitro assay, acetaminophen formation in the hepatic microsomes of ZJ-treated rats was investigated to assess CYP1A2 activity. Our results demonstrated that the treatment with the water and ethanolic extracts of ZJ decreased the plasma concentration of phenacetin and increased the plasma concentration of acetaminophen, resulting in a 43.2% and 15.5% reduction in the AUC0-120 of phenacetin, respectively, and a 53.2% and 64.9% increase in the AUC0-120 of acetaminophen, respectively after intravenous administration. The water or ethanolic extract of ZJ significantly increased the clearance of phenacetin and acetaminophen formation in hepatic microsomes. In conclusion, ZJ extracts displayed effects on the pharmacokinetics of phenacetin and increased the CYP1A2 activity in rats. Therefore, precaution on drug-drug interactions should be taken when ZJ is co-administered with drugs metabolized by CYP1A2, which may result in decreased concentrations of these drugs.

关键词： ziziphusjujuba CYP1A2 Phenacetin Aeetaminophen Hepatic microsomes Plant drug-drug interactions

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