Ginkgolide B induces CYP3 A4 expression through activation of human pregnane X receptor / 中国药理学通报

ABSTRACT

Aim To study the induction effect of Ginkgolide B on CYP3A4,and further verify the role of pregnane X receptor in CYP3 A4 induction expres-sion. Methods With different concentrations of Ginkgolide B treatment on LS174T cells,the CYP3A4 mRNA expression was detected by Q-PCR assay,fur-ther PXR-CYP3 A4 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, CYP3 A4 mRNA and protein were detected in the con-dition 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 en-hance the transcriptional activity of PXR in a concen-tration-dependent manner.Under conditions of low ex-pression of PXR ,Ginkgolide B could also increase ex-pression of CYP3A4,but the induction folds were low-er than those of normal PXR group.Conclusion Ginkgolide B can signicantly up-regulate CYP3 A4 ex-pression via the PXR-CYP3 A4 pathway,and it has no effects on PXR gene expression.