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-fluorouraci...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.展开更多
We build a strategic trading model where the overconfident trader earns more than the rational trader and the mechanism for this result differs from that of Kyle and Wang(1997). In this paper, discretionary and nondis...We build a strategic trading model where the overconfident trader earns more than the rational trader and the mechanism for this result differs from that of Kyle and Wang(1997). In this paper, discretionary and nondiscretionary liquidity traders coexist. The overconfident insider is less worried by the market maker and thus induces a lower liquidity cost. In this way, he attracts all the trading from the discretionary liquidity traders, which enables the survival of the overconfident trader.展开更多
基金Supported by the National Natural Science Foundation of China(81202583)the Education Department of Jiangxi Province(GJJ12145)+1 种基金Research Fund Project for Traditional Chinese Medicine of the Health Department of Jiangxi Province(2012A137)the Department of Science and Technology of Jiangxi Province(20151BBG70214)
文摘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.
基金Supported by National Natural Science Foundation of China(Grant No.11301563)the Program for innovation Research in Central University of Finance and Economics+1 种基金Beijing Municipal Education Commission Scientific Research PlanSocial Science Plan General Project(Grant No.KM201710017004)
文摘We build a strategic trading model where the overconfident trader earns more than the rational trader and the mechanism for this result differs from that of Kyle and Wang(1997). In this paper, discretionary and nondiscretionary liquidity traders coexist. The overconfident insider is less worried by the market maker and thus induces a lower liquidity cost. In this way, he attracts all the trading from the discretionary liquidity traders, which enables the survival of the overconfident trader.
