Clinical Pharmacology Institute, Nanchang University, Nanchang, China.
School of Pharmaceutical Engineering, Chongqing Chemical Industry Vocational College, Chongqing, China.
Phytother Res. 2019 Apr;33(4):968-975. doi: 10.1002/ptr.6290. Epub 2019 Jan 17.
Panaxytriol (PXT) is one of the major effective components of red ginseng and Shenmai injection. The present study aimed to explore the effect of PXT on cytochrome P450 3A4 (CYP3A4) based on the pregnane X receptor (PXR)-CYP3A4 regulatory pathway in HepG2 cells and hPXR-overexpressing HepG2 cells treated with PXT for different time periods using quantitative polymerase chain reaction, Western blot, and dual-luciferase reporter gene assays. PXT could upregulate the levels of PXR and CYP3A4 mRNA in HepG2 cells treated with PXT for 1 hr, with no impact on the expression of their protein levels. The expression levels of both PXR and CYP3A4 mRNA and protein in HepG2 cells treated with PXT for 24 hr increased in a concentration-dependent manner. The effects of PXT on the expression of PXR and CYP3A4 mRNA and protein in hPXR-overexpressing HepG2 cells were similar to those in HepG2 cells. Moreover, the influence trend of PXT on CYP3A4 was consistent with that of PXR in HepG2 cells and hPXR-overexpressing HepG2 cells. The dual-luciferase reporter gene assay in HepG2 cells further demonstrated that PXT treatment for specific time periods could significantly induce the expression of CYP3A4 mediated by the PXR regulatory pathway.
人参三醇（PXT）是红参和参麦注射液的主要有效成分之一。本研究旨在通过定量聚合酶链反应、Western blot 和双荧光素酶报告基因检测，探讨 PXT 对细胞色素 P4503A4（CYP3A4）基于孕烷 X 受体（PXR）-CYP3A4 调控途径的影响，研究 PXT 对 HepG2 细胞和不同时间点用 PXT 处理的 hPXR 过表达 HepG2 细胞的影响。PXT 可在 1 小时内上调 HepG2 细胞中 PXR 和 CYP3A4 mRNA 的水平，而对其蛋白水平无影响。PXT 处理 24 小时后 HepG2 细胞中 PXR 和 CYP3A4 mRNA 和蛋白的表达水平呈浓度依赖性增加。PXT 对 hPXR 过表达 HepG2 细胞中 PXR 和 CYP3A4 mRNA 和蛋白表达的影响与 HepG2 细胞相似。此外，PXT 对 CYP3A4 的影响趋势与 HepG2 细胞和 hPXR 过表达 HepG2 细胞中 PXR 的影响趋势一致。HepG2 细胞中的双荧光素酶报告基因检测进一步表明，PXT 处理特定时间可显著诱导 PXR 调控途径介导的 CYP3A4 表达。
