title: Dose-response of oridonin on hepatic cytochromes P450 mRNA expression and activities in mice.
abstract: BACKGROUND
  Oridonin, the major terpene found in Rabdosia rubescens, is widely used as a dietary supplement or therapeutic drug. The effects of oridonin on drug processing genes, such as cytochrome P450 and nuclear receptors, were still unclear. Therefore, the present study investigated the influence of oridonin on the hepatic drug metabolizing system to evaluate the safety through its drug interaction potential.
  
  
  METHODS
  In this study, eight-week-old male C57BL/6 mice were treated oridonin orally (0, 25, 50, 100, 200 mg/kg, i.g.) for 15 days. The effects of oridonin on major Cyps in mice livers were examined at both the mRNA and enzyme activity levels.
  
  
  RESULTS
  In general, there are no significant influence of various dose of oridonin on mice liver function. However, oridonin significantly increased Cyps (1a, 2a, 2d, 2e, 2c and 3a family) mRNA expression. In addition, it could induce Cyps activity in microsome incubation at maximum dosage. To our knowledge, it is the first time to identify oridonin as a Cyps inducer in vivo. It also promotes the expression of CAR, PXR and POR.
  
  
  CONCLUSIONS
  These results indicate that, if studies in mice extrapolate to humans by orthologous genes, oridonin appears to be a risk to herb-drug interactions due to its induction effects on drug processing genes expression and activation.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
authors.forename: Yi-wen
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China; Department of Pharmacy, Changsha Medical University, Changsha 410219, China.
authors.forename: Mei-hua
authors.initials: MH
authors.lastname: Bao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Qu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China. Electronic address: hhzhou2003@163.com.
authors.forename: Hong-hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000284:Administration, Oral; D000818:Animals; D065693:Cytochrome P-450 Enzyme Inducers / Q000008:administration & dosage / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D045786:Diterpenes, Kaurane / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D041743:Herb-Drug Interactions; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D065693:Cytochrome P-450 Enzyme Inducers; D045786:Diterpenes, Kaurane; D012333:RNA, Messenger; C011959:oridonin; D003577:Cytochrome P-450 Enzyme System
keywords: Cytochrome P450; Herb–drug interaction; Nuclear receptors; Oridonin