title: Effects of Bu-Zhong-Yi-Qi-Tang on hepatic drug-metabolizing enzymes and plasma tolbutamide concentration in rats.
abstract: BACKGROUND
  Bu-Zhong-Yi-Qi-Tang (BT) is the dry powder derived from the aqueous extract of a mixture of 10 medicinal herbs. It is a traditional Chinese medicine being used for the treatment of various immune-related diseases.
  
  
  OBJECTIVE
  To investigate the effect of BT on hepatic drug-metabolizing enzymes and its effect on plasma concentrations of tolbutamide, a substrate of CYP2C, in rats.
  
  
  METHODS
  EXP 1: Thirty-two male Wistar rats were divided into four groups. Rats were fed a control diet and a control diet containing 1, 2.5 and 5% (w/w) of BT, respectively, for eight weeks. The activities of the major CYP and Phase II conjugating enzymes in rat liver microsomes as well as the antioxidant system in rat liver were assessed. Exp 2: Male Wistar rats were fed a control diet or a control diet containing 2.5% of BT, respectively, for eight weeks. A single 20-mg/kg oral dose of tolbutamide was then administered to each rat. Plasma samples were collected from each rat at 0.5, 1, 2, 4 and 8h after dosing. The concentrations of tolbutamide and glucose level in plasma were determined by high-performance liquid chromatography-mass spectrometer (HPLC/MS) and enzymatic method, respectively.
  
  
  RESULTS
  Significant decrease in microsomal CYP2C-catalyzed diclofenac 4-hydroxylation in the liver of rats fed the BT diet was observed. Increased UDP-glucuronosyltransferase (UGT) and glutathione S-transferase (GST) activities were also observed in the liver of rats fed the diet containing 2.5 and 5% of BT. Immunoblot analyses also showed decreases of CYP2C11 proteins in the liver of BT fed rats. In addition, rats fed the 2.5% BT diet for eight weeks had no effects on the disposition of tolbutamide and reduction of glucose level in plasma after orally administered of tolbutamide.
  
  
  CONCLUSIONS
  Rats fed the BT diet for eight weeks may decrease CYP2C enzyme activity and protein expression and increase Phase II conjugating enzyme activities in liver. However, BT may not affect the disposition and efficacy of tolbutamide.
authors.affiliation: Department of Nutrition, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan. htyao@mail.cmu.edu.tw
authors.forename: Hsien-Tsung
authors.initials: HT
authors.lastname: Yao
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Chang
authors.forename: Naoto
authors.initials: N
authors.lastname: Uramaru
authors.forename: Yoko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kitamura
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.forename: Chong-Kuei
authors.initials: CK
authors.lastname: Lii
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D059305:Diet, High-Fat; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014044:Tolbutamide / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D001786:Blood Glucose; D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; C402943:bu-zhong-yi-qi-tang; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D005978:Glutathione