title: Curculigo orchioides (Xian Mao) modifies the activity and protein expression of CYP3A in normal and Kidney-Yang Deficiency model rats.
abstract: OBJECTIVE
  In Chinese medicine clinics, traditional Chinese herbs are used to treat disorders of Yin and Yang balance, including Kidney-Yang Deficiency. The activity of the hepatic cytochrome P450 3A (CYP3A) is closely associated with body status. The aim of the present study is to investigate CYP3A enzymatic activity and CYP3A4 protein expression using a Kidney-Yang Deficiency rat model and furthermore to investigate the intervention effects of the Pungent-hot herb Xian Mao. This work contributes rationale for personalized medicine and enhances our understanding of herb-drug interactions.
  
  
  METHODS
  Rats were randomly divided into three groups: the model group, the Xian Mao group and the intervention group (model rats treated with Xian Mao). The model rats were given an intramuscular injection of hydrocortisone for 14 days, and the control rats were given normal saline. The Xian Mao group consisted of normal rats treated with Xian Mao by oral gavage for 7 days. The intervention group was given Xian Mao for 7 days after treatment with hydrocortisone. The activity of CYP3A was detected by using the erythromycin-N-demethylase method. CYP3A4 protein expression level was detected by Western-blot.
  
  
  RESULTS
  CYP3A enzymatic activity in the Kidney-Yang Deficiency rat was decreased by 44% compared to normal animals. The relative CYP3A4 protein expression level of the Kidney-Yang Deficiency rat (mean value 0.663±0.188) was 20% lower than that of normal rat (0.830±0.199). The in vitro data showed that CYP3A activity was significantly (P<0.001) inhibited (decreased by 59%) by Xian Mao concentrations of 1mg/mL. The in vivo data also showed that CYP3A activity was significantly decreased in the rats treated with the three doses of Xian Mao. The CYP3A4 protein expression was significantly decreased by Xian Mao treatment at the high and intermediate doses (30 and 20 g/kg, respectively) compared with the normal group. However, the intervention group (the Kidney-Yang Deficiency rat treated with Xian Mao at 20 and 30 g/kg) showed an increased CYP3A activity and CYP3A4 protein expression compared with the herb-untreated model rats.
  
  
  CONCLUSIONS
  CYP3A enzymatic activity and CYP3A4 protein expression could be inhibited by Xian Mao. The CYP3A activity and CYP3A4 expression in the Kidney-Yang Deficiency model rat were lower than that of normal rat but this deficiency could be rescued by treatment with Xian Mao.
authors.affiliation: Department of Biological Pharmaceutics, School of Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. wchunmei@126.com
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Wang
authors.forename: Song-Yao
authors.initials: SY
authors.lastname: Xu
authors.forename: Shuo
authors.initials: S
authors.lastname: Lai
authors.forename: Di
authors.initials: D
authors.lastname: Geng
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Huang
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Huo
mesh_terms: D000818:Animals; D031408:Curculigo; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D018517:Plant Roots; D051381:Rats; D017207:Rats, Sprague-Dawley; D016711:Yang Deficiency / Q000201:enzymology*
chemical_list: D004365:Drugs, Chinese Herbal; D003577:Cytochrome P-450 Enzyme System; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A