Mechanism of Berberine in the Regulation of CYP3A4 and P-gp via PXR Signaling Pathway / 中国药师

ABSTRACT

Objective: To investigate the regulation of CYP3A4 and P-gp by berberine hydrochloride ( BBR) via pregnane X re-ceptor (PXR) pathway. Methods: pLKO. 1-PXR vector, a lentivirus plasmid expressing PXR shRNA, was packaged into 293T cells. Human hepatoma (HepG2) cells were infected with the lentivirus and the cell clones stably expressing PXR shRNA were selected by puromycin according to pLKO. 1 vector characteristics. Real-time RT-PCR and Western blot were used to evaluate CYP3A4 and P-gp mRNA and protein in berberine treated HepG2 cells and PXR-silenced HepG2 cells. Results: The PXR expression in PXR silenced cells significantly decreased (P<0.01) when compared with that in HepG2 cells, while there was no significant difference (P >0. 05) in the expression of CYP3A4 and P-gp between the groups. Compared with that in HepG2 cells, the inhibition of berberine on the mRNA and protein expression of CYP3A4 and P-gp in PXR-silenced HepG2 cells was weakened (P<0. 05 or P<0. 01). Conclu-sion Berberine can regulate the expression of CYP3A4 and P-gp via PXR signaling pathway, while it is not the only one.