Chinese Medical Sciences Journal ›› 2015, Vol. 30 ›› Issue (4): 218-225.doi: 10.1016/S1001-9294(16)30004-9

• Original Article • Previous Articles     Next Articles

Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin In Vivo and Vitro

Jin-hua Wen, Xiao-hua Wei, Xiang-yuan Sheng, De-qing Zhou, Hong-wei Peng, Yan-ni Lu, Jian Zhou   

  1. Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China
  • Received:2015-05-19 Online:2015-12-20 Published:2015-12-20
  • Supported by:
    △Supported by the National Natural Science Foundation of China (81202583), the Education Department of Jiangxi Province (GJJ12145) and Research Fund Project for Traditional Chinese Medicine of the Health Department of Jiangxi Province (2012A137), and the Department of Science and Technology of Jiangxi Province (20151BBG70214)

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) Ⅱ-BCRP421CC (wild type) cells and MDCKⅡ-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.Conclusion 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.

Key words: ursolic acid, breast cancer resistance protein, rosuvastatin, transport

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