title: Effect of Yin-Zhi-Huang on up-regulation of Oatp2, Ntcp, and Mrp2 proteins in estrogen-induced rat cholestasis.
abstract: BACKGROUND
  Yin-Zhi-Huang (YZH), a prescription of traditional Chinese medicine, is widely used to treat neonatal jaundice or cholestasis.
  
  
  OBJECTIVE
  This study investigates the regulatory effect of YZH on the localization and expression of organic anion transporting polypeptides 2 (Oatp2), Na(+)-taurocholate co-transporting polypeptide (Ntcp), multidrug-resistance-associated protein 2 (Mrp2), and bile salt export pump (Bsep) in estrogen-induced cholestasis rats.
  
  
  METHODS
  Cholestasis model rats were induced via subcutaneous injection of estradiol benzoate (EB, 5 mg/kg/d) for 5 d. Other EB-induced rats were treated with saline (2 ml) or YZH (1.5 g/kg, two times a day) for 7, 14, and 21 d. The biochemical and pathologic examinations were performed. Moreover, the localization and expression of Oatp2, Ntcp, Mrp2, and Bsep were determined by immunohistochemisty and Western blotting, respectively.
  
  
  RESULTS
  YZH treatment could significantly decrease the serum total bile acids (TBA) (4.9 ± 0.6-2.8 ± 0.8) and direct bilirubin (DBIL) (2.6 ± 0.7-1.0 ± 0.1) levels, improve the histological disorganization, and, respectively, increase the expression of Oatp2 and Ntcp by 46% and 28% compared with saline-treated (p < 0.05) rats at 14 d. The expression of Mrp2 increased by 45% was observed in YZH treated compared with saline-treated (p < 0.05) rats at 7 d. However, there was a little change in the expression of Bsep (p > 0.05) after YZH treatment for 7, 14, and 21 d.
  
  
  CONCLUSIONS
  In conclusion, the therapeutic effect of YZH to cholestasis could be attributed to the regulation of Oatp2, Ntcp, Mrp2, and Bsep.
authors.affiliation: Department of Pharmacy, The First Hospital of Lanzhou University , Lanzhou , China and.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhi
authors.initials: Z
authors.lastname: Rao
authors.forename: Hongyan
authors.initials: H
authors.lastname: Qin
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wei
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Ren
authors.forename: Liting
authors.initials: L
authors.lastname: Zhou
authors.forename: Xin'an
authors.initials: X
authors.lastname: Wu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000818:Animals; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D004967:Estrogens / Q000633:toxicity*; D008297:Male; D027361:Organic Anion Transporters / Q000096:biosynthesis*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000096:biosynthesis*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D004365:Drugs, Chinese Herbal; D004967:Estrogens; D027361:Organic Anion Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; C503597:Slco1a4 protein, rat; D027981:Symporters; C070600:yin zhi huang; C071908:sodium-bile acid cotransporter
keywords: Estradiol benzoate; neonatal jaundice; traditional Chinese medicine; transporter