title: Effects of unprocessed versus vinegar-processed Schisandra chinensis on the activity and mRNA expression of CYP1A2, CYP2E1 and CYP3A4 enzymes in rats.
abstract: BACKGROUND
  Schisandra chinensis (SC) is a well-known traditional Chinese herbal medicine that has been used in clinical practices for thousands of years. However, the differences between the effects of unprocessed and vinegar-processed Schisandra chinensis (VSC) on cytochrome P450 (CYP450) activities are poorly understood.
  
  
  OBJECTIVE
  To evaluate the differences between processed and unprocessed SC on the metabolism of CYP1A2, CYP2E1 and CYP3A4 substrates in rats using a cocktail method based on a developed and validated HPLC method. We also investigate the influence of processing on the levels of CYP mRNA.
  
  
  METHODS
  Three probe substrates (theophylline, dapsone and chlorzoxazone) were delivered simultaneously into rats treated with single or multiple doses of processed or unprocessed SC extract. The plasma concentrations of the three probes were profiled by HPLC, and their corresponding pharmacokinetic parameters were calculated. Real-time RT-PCR was performed to determine the effects of processed and unprocessed SC on the mRNA expression of CYP1A2, CYP2E1 and CYP3A4 in the liver.
  
  
  RESULTS
  Treatment with single or multiple doses of either extract of SC induced CYP3A4 enzyme activity and inhibited CYP1A2 enzyme activity in rats. Furthermore, the inhibitory effect of SC was more potent after vinegar processing than without vinegar processing. CYP2E1 enzyme activity was induced after treatment with a single dose but was inhibited after multiple doses. The mRNA expression results were in accordance with the pharmacokinetic results.
  
  
  CONCLUSIONS
  These results provide useful scientific data for the safe clinical application of either extract of SC in combination with other drugs, which should lack the side effects induced by other herb-drug interactions.
authors: The Key Laboratory of Chinese Herbal Medicine Processing of Jiangsu Province, Nanjing, 210046, PR China.
authors: Tao
authors: T
authors: Su
authors: Chunqin
authors: C
authors: Mao
authors: Fangzhou
authors: F
authors: Yin
authors: Zhiling
authors: Z
authors: Yu
authors: Ying
authors: Y
authors: Lin
authors: Yu
authors: Y
authors: Song
authors: Tulin
authors: T
authors: Lu
mesh_terms: D019342:Acetic Acid / Q000737:chemistry*; D000818:Animals; D002753:Chlorzoxazone / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D003580:Cytochromes / Q000096:biosynthesis / Q000378:metabolism; D003622:Dapsone / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D004790:Enzyme Induction; D041743:Herb-Drug Interactions; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D032141:Schisandra / Q000737:chemistry*; D013379:Substrate Specificity; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D003580:Cytochromes; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D003622:Dapsone; D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline; D019392:Cytochrome P-450 CYP2E1; C017170:Cyp1a2 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D002753:Chlorzoxazone; D019342:Acetic Acid