[Kaempferol activates human steroid and xenobiotic receptor-mediated cytochrome P450 3A4 transcription]

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006 Jan;35(1):14-7. doi: 10.3785/j.issn.1008-9292.2006.01.003.
[Article in Chinese]

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / pathology
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Cytochrome P-450 Enzyme System / genetics*
  • Dose-Response Relationship, Drug
  • Genes, Reporter
  • Humans
  • Kaempferols / pharmacology*
  • Liver Neoplasms / pathology*
  • Pregnane X Receptor
  • Receptors, Steroid / metabolism*
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Kaempferols
  • Pregnane X Receptor
  • Receptors, Steroid
  • kaempferol
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human