Ginkgolide B induces CYP3A4 expression through activation of human pregnane X receptor

Aim: To study the induction effect of Ginkgolide B on CYP3A4, and further verify the role of pregnane X receptor in CYP3A4 induction expression. Methods: With different concentrations of Ginkgolide B treatment on LS174T cells, the CYP3A4 mRNA expression was detected by Q-PCR assay, further PXR-CYP3A4 stable translation HepG2 cell lines were used to test the effect of Ginkgolide B on activity of PXR by reporter gene screening assay. CYP3A4 protein expression was detected by Western blot. PXR was knocked down with transfected with siRNA, CYP3A4 mRNA and protein were detected in the condition of PXR low expression. Results: The results revealed that the level of CYP 3 A 4 gene and protein expression were significantly increased by Ginkgolide B, and there was no induction effect on PXR. Reporter gene screening showed that Ginkgolide B could enhance the transcriptional activity of PXR in a concentration-dependent manner. Under conditions of low expression of PXR , Ginkgolide B could also increase expression of CYP3A4, but the induction folds were lower than those of normal PXR group. Conclusion: Ginkgolide B can signicantly up-regulate CYP3A4 expression via the PXR-CYP3A4 pathway, and it has no effects on PXR gene expression.