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Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin
In Vivo andVitro △- Affiliations：
Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China
- Author bio：
- Funds：△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).
DOI：
中图分类号：-
网络出版日期：2015-08-20，
纸质出版日期：2015-08
- Accepted：
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Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin
In Vivo andVitro △[J]. 中国医学科学杂志（英文版）, 2015,30(4):218-225.Wen* Jin-hua, Wei Xiao-hua, Sheng Xiang-yuan, et al. Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin
In Vivo andVitro △[J]. Chinese medical sciences journal, 2015, 30(4): 218-225.Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin
In Vivo andVitro △[J]. 中国医学科学杂志（英文版）, 2015,30(4):218-225. DOI：Wen* Jin-hua, Wei Xiao-hua, Sheng Xiang-yuan, et al. Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin
In Vivo andVitro △[J]. Chinese medical sciences journal, 2015, 30(4): 218-225. DOI：
摘要
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
.
关键词
Keywords
references
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