Effect of panaxytriol on cytochrome P450 3A4 via the pregnane X receptor regulatory pathway

Abstract

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.

Research progress of ginseng in the treatment of gastrointestinal cancers

“…High concentrations of PNT (80 μmol/L) can regulate HCC HepG2 cytochrome P3A4 (CYP3A4) expression through constitutive androstane receptor (CAR), The effects of CAR and pregnane X receptor (PXR) have an interactive dialogue, and after regulation, CAR can inhibit the PXR-CYP3A4 pathway ( Hu, 2018 ; Hu Q et al, 2019 ). PNT triol upregulationes CYP3A4 in human HCC HepG2 cells through the nuclear receptor PXR and upregulates PXR and CYP3A4 mRNA and protein expression after 24 h of intervention ( Wu, 2017 ; Wu et al, 2019 ). In both human HCC HepG2 and Huh-7 cells, PNT upregulated the expression of the target gene CYP3A4 by attenuating the binding of PXR to HSP90α and promoting PXR-RXRα binding.…”