Panax Notoginseng Saponins Increases the Blood Concentration of Nifedipine by Inhibiting CYP3A4 Enzyme through PXR-and CAR-Mediated Pathway  

作　　者：Qiu-Hong Li Jiao Zhao Ai-Xia Ju Yong Hu Qing-Song Qie Hong-Bin Xiao Guang Xu Xi-Jun Wang 

机构地区：[1]Clinical Pharmacy Laboratory,Department of Pharmaceutics,School of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin,China [2]9601 Medical Center Drive,Rockville,MD,USA

出　　处：《World Journal of Traditional Chinese Medicine》2021年第3期332-338,共7页世界中医药杂志（英文）

基　　金：supported by Heilongjiang Natural Science Foundation(No.LH2019H107);Innovation Fund for postgraduates of Heilongjiang University of Chinese Medicine(No.2020yjscx058)。

摘　　要：Objective:To explore the mechanism underlying the effect of Panax notoginseng saponins(PNS)on the pharmacokinetics of nifedipine(NF)in rats.Materials and Methods:Twenty-four rats were randomly divided into blank(BL)group,PNS group,NF group,and PNS+NF group,with six rats in each group.Noncompartmental analysis and t-test were carried out to determine the difference between the pharmacokinetic parameters of NF in different groups.CYP3 A4 enzyme activity was calculated using the probe drug method.The mRNA and protein contents of CYP3 A4,nuclear receptor CAR,and PXR in rat liver were quantitatively analyzed by qRT-PCR and Western blot.Results:After the rats were treated with the combination of PNS and NF,the plasma concentration,half-life,peak time,and area under the concentration-time curve of NF increased,whereas the clearance rate decreased.The inhibitory effect on CYP3 A4 enzyme activity was in the following order:PNS+NF group(strongest)>PNS group>NF group,and BL group(weakest).Similar changes were observed for the inhibitory effect on CYP3 A4,CAR,and PXR mRNA and protein content,and the order was as follows:PNS+NF group(weakest)<PNS group<NF group,and BL group(strongest).Conclusion:In combination with NF,PNS may inhibit the mRNA and protein expression of nuclear receptor CAR and PXR and the activity of CYP3 A4 enzyme,slowing down the pharmacokinetics of NF in rats,increasing its blood concentration,and enhancing the therapeutic effect of NF.

关 键 词：CAR CYP3A4 NIFEDIPINE Panax notoginseng saponins PHARMACOKINETICS PXR 

分 类 号：R285[医药卫生—中药学]