title: Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin In Vivo and Vitro.
abstract: OBJECTIVE
  To evaluate whether ursolic acid can inhibit breast cancer resistance protein (BCRP)-mediated transport of rosuvastatin in vivo and in vitro.
  
  
  METHODS
  Firstly, we explored the pharmacokinetics of 5-fluorouracil (5-FU, a substrate of BCRP) in rats in the presence or absence of ursolic acid. Secondly, we studied the pharmacokinetics of rosuvastatin in rats in the presence or absence of ursolic acid or Ko143 (inhibitor of BCRP). Finially, the concentration-dependent transport of rosuvastatin and the inhibitory effects of ursolic acid and Ko143 were examined in Madin-Darby Canine Kidney (MDCK) 2-BCRP421CC (wild type) cells and MDCK2-BCRP421AA (mutant type) cells.
  
  
  RESULTS
  As a result, significant changes in pharmacokinetics parameters of 5-FU were observed in rats following pretreatment with ursolic acid. Both ursolic acid and Ko143 could significantly affect the pharmacokinetics of rosuvastatin. The rosuvastatin transport in the BCRP overexpressing system was increased in a concentration-dependent manner. However, there was no statistical difference in BCRP-mediated transport of rosuvastatin betweent the wild type cells and mutant cells. The same as Ko143, ursolic acid inhibited BCRP-mediated transport of rosuvastatin in vitro.
  
  
  CONCLUSIONS
  Ursolic acid appears to be a potent modulator of BCRP that affects the pharmacokinetic of rosuvastatin in vivo and inhibits the transport of rosuvastatin in vitro.
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Jin-hua
authors.initials: JH
authors.lastname: Wen
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Wei
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Xiang-yuan
authors.initials: XY
authors.lastname: Sheng
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: De-qing
authors.initials: DQ
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Hong-wei
authors.initials: HW
authors.lastname: Peng
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Yan-ni
authors.initials: YN
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D054659:Diketopiperazines; D006576:Heterocyclic Compounds, 4 or More Rings; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium / Q000493:pharmacokinetics*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000241:Adenosine; D054659:Diketopiperazines; D006576:Heterocyclic Compounds, 4 or More Rings; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D014315:Triterpenes; D000097245:Ursolic Acid; C541506:3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino(1',2'-1,6)pyrido(3,4-b)indol-3-yl)propionic acid tert-butyl ester; C489249:Abcg2 protein, rat