首页|期刊导航|世界中医药杂志（英文版）|Panax Notoginseng Saponins Increases the Blood Concentration of Nifedipine by Inhibiting CYP3A4 Enzyme through PXR- and CAR-Mediated Pathway
世界中医药杂志（英文版）2021，Vol.7Issue(3)：332-338,7.DOI:10.4103/wjtcm.wjtcm_52_21
Panax Notoginseng Saponins Increases the Blood Concentration of Nifedipine by Inhibiting CYP3A4 Enzyme through PXR- and CAR-Mediated Pathway
Panax Notoginseng Saponins Increases the Blood Concentration of Nifedipine by Inhibiting CYP3A4 Enzyme through PXR? and CAR?Mediated Pathway
摘要
Abstract
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. CYP3A4 enzyme activity was calculated using the probe drug method. The mRNA and protein contents of CYP3A4, 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 CYP3A4 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 CYP3A4, 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 CYP3A4 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/PXRKey words
CAR/CYP3A4/nifedipine/Panax notoginseng saponins/pharmacokinetics/PXR引用本文复制引用
Qiu?Hong Li,Jiao Zhao,Ai?Xia Ju,Yong Hu,Qing?Song Qie,Hong?Bin Xiao,Guang Xu,Xi?Jun Wang..Panax Notoginseng Saponins Increases the Blood Concentration of Nifedipine by Inhibiting CYP3A4 Enzyme through PXR- and CAR-Mediated Pathway[J].世界中医药杂志（英文版）,2021,7(3):332-338,7.基金项目
This work was supported by Heilongjiang Natural Science Foundation?(No.LH2019H107)and Innovation Fund for postgraduates of Heilongjiang University of Chinese Medicine?(No.?2020yjscx058). （No.LH2019H107）
