人参皂苷F1通过激活孕烷X受体诱导CYP3 A4的表达

摘要

目的：探索人参皂苷F1( ginsenoside F1)是否通过激活孕烷X受体(PXR)实现对CYP3A4基因表达及酶活性的诱导作用。方法利用本实验室构建的PXR-CYP3A4稳定转染HepG2工程细胞株结合荧光素酶报告基因技术，检测人参皂苷F1对PXR的转录激活效应；用不同浓度的人参皂苷F1处理LS174T细胞，并通过Q-PCR和酶活性试剂盒检测CYP3A4的mRNA表达和酶活性变化。结果不同浓度人参皂苷F1作用于LS174T细胞以后，可以浓度依赖性地诱导CYP3A4 mRNA 水平的表达，并且增强其酶活性；同时， PXR-CYP3A4稳定转染HepG2工程细胞株结合荧光素酶报告基因检测结果亦表明，人参皂苷F1能够浓度依赖性地增强PXR的转录激活效应。结论本研究揭示了人参皂苷F1可诱导CYP3A4的基因表达并增强其酶活性，这一过程可能与人参皂苷F1对孕烷X受体的激活有关。%Aim To study the effect of ginsenoside F1 on the enzyme activity and expression of gene of CYP3 A4 through activation of pregnane X receptor ( PXR ) . Methods With different concentrations of ginsenoside F1 treated on LS174T cells, the expression of CYP3A4 mRNA was determined by Q-PCR, and the enzyme activity was measured by P450-GloTM CYP3A4 assay according to the manufacturer′s instructions, fur-ther PXR-CYP3 A4 stable translation HepG2 cell lines were used to test ginsenoside F1 activates PXR by re-porter gene screening assay. Results The results re-vealed that the levels of CYP3 A4 gene and protein ex-pression were significantly increased by ginsenoside F1 in a concentration-dependent manner. At the same time, reporter gene screening showed that ginsenoside F1 could also enhance the transcriptional activity of PXR. Conclusion Ginsenoside F1 can significantly up-regulate the gene expression and enzyme activity of CYP3A4 via the PXR-CYP3A4 pathway.