title: Effects of Ziziphus jujuba fruit extracts on cytochrome P450 (CYP1A2) activity in rats.
abstract: 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 Ziziphus jujuba fruit (ZJ) 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(-1)) 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.
authors.affiliation: Laboratory of Integrated Acupuncture and Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Jing
authors.affiliation: Jiangsu Provincial Institute of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Peng
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: dja@njutcm.edu.cn.
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
mesh_terms: D000082:Acetaminophen / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000378:metabolism*; D005638:Fruit; D041743:Herb-Drug Interactions; D008099:Liver / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver; D010615:Phenacetin / Q000378:metabolism / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D031957:Ziziphus
chemical_list: D003580:Cytochromes; D010936:Plant Extracts; D000082:Acetaminophen; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D010615:Phenacetin
keywords: Acetaminophen; CYP1A2; Hepatic microsomes; Phenacetin; Plant drug-drug interactions; Ziziphus jujuba