[Kaempferol activates human steroid and xenobiotic receptor-mediated cytochrome P450 3A4 transcription].
To investigate whether kaempferol stimulates pregnane X receptor (PXR)-mediated transcription of CYP3A4.



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.



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.



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.
Institute of Medical Nutrition and Food Hygiene, Zhejiang University, Hangzhou 310031, China.
Dong-ying
DY
Liu
Hui-juan
HJ
Zhu
Yi-fan
YF
Zheng
Xin-qiang
XQ
Zhu
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D044949:Kaempferols; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C006552:kaempferol; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human