Kaempferol activates human steroid and xenobiotic receptor-mediated cytochrome P450 3A4 transcription.
- Author:
Dong-ying LIU
1
;
Hui-juan ZHU
;
Yi-fan ZHENG
;
Xin-qiang ZHU
Author Information
- Publication Type:Journal Article
- MeSH: Carcinoma, Hepatocellular; pathology; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; biosynthesis; genetics; Dose-Response Relationship, Drug; Genes, Reporter; Humans; Kaempferols; pharmacology; Liver Neoplasms; pathology; Receptors, Steroid; metabolism; Transcription, Genetic; Transfection; Tumor Cells, Cultured
- From: Journal of Zhejiang University. Medical sciences 2006;35(1):14-17
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate whether kaempferol stimulates pregnane X receptor (PXR)-mediated transcription of CYP3A4.
METHODSTransient 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.
RESULTSKaempferol 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.
CONCLUSIONKaempferol may be a human CYP3A4 gene inducer through PXR, and may affect the metabolism of a large number of substrates of CYP3A4 simultaneously taken.
