Objective: To investigate whether kaempferol stimulates pregnane X receptor (PXR)-mediated transcription of CYP3A4.
Methods: Transient cotransfection reporter gene assay was performed with PXR expression plasmid and a reporter plasmid containing the XREs in the CYP3A4 gene promoter in HepG(2)cells.
Results: Kaempferol activated PXR-mediated transcription of CYP3A4 in a dose, time-dependent manner. In the dose-response study, kaempferol exposure at concentrations of 1.0 x 10(-3), 1.0 x 10(-2), 0.1, 1.0 and 10.0 mol/L for 24 h increased CYP3A4 transcription by (1.31+/-0.27), (1.45+/-0.36), (1.96+/-0.50), (2.90+/-1.07) and (7.93+/-0.75) fold, respectively compared with 0.1% DMSO (P<0.05). The results from time-course study showed that after 48 h exposure 1.0 and 10.0 mol/L of kaempferol enhanced the transcription of CYP3A4 by (3.73+/-1.21) fold and (8.42+/-1.47) fold, respectively.
Conclusion: Kaempferol may be a human CYP3A4 gene inducer through PXR, and may affect the metabolism of a large number of substrates of CYP3A4 simultaneously taken.
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