[Human pregnane X receptor-mediated transcriptional regulation of cytochrome P450 3A4 by some phytochemicals].
To test the effect on human pregnane X receptor (hPXR)-mediated transcription regulation of CYP3A4 by five selected phytochemicals.



Transient cotransfection reporter gene assays in HepG(2) cells were performed with the hPXR expression plasmid and the reporter gene plasmid which contains XRE in the promoter of CYP3A4 linked to luciferase.



In the dose-effect study, soybean isoflavone, luteolin and curcumin induced the CYP3A4 transcription via PXR in an evident dose-dependent manner, but isorhamnetin and rutin did not. The inducibility of soybean isoflavone, luteolin and curcumin was also increased in concentrations between 1 micromol/L and 50 micromol/L, 24 h after induction, 50 micromol/L soybean isoflavone, luteolin and curcumin exhibited a 5.46-fold, 2.87-fold, and 2.07-fold increase respectively, compared with 0.1% DMSO treated cells. In the time-effect study, 10 micromol/L and 50 micromol/L soybean isoflavone, luteolin and curcumin induced CYP3A4 transcription between 12 h and 48 h, the strongest induction appeared in 48 h. 48 h after induction, 50 micromol/L soybean isoflavone, luteolin and curcumin exhibited a 6.72-fold, 3.24-fold, and 2.13-fold increase respectively, compared with 0.1% DMSO treated cells.



Three phytochemicals, i.e. soybean isoflavone, luteolin and curcumin stimulate the PXR-mediated transcription of CYP3A4. Isorhamnetin and rutin have no effect on the CYP3A4 transcription via PXR.
Institute of Medical Nutrition and Food Hygiene, Zhejiang University, Hangzhou 310031, China.
Dong-ying
DY
Liu
Min
M
Yang
Hui-juan
HJ
Zhu
Yi-fan
YF
Zheng
Xin-qiang
XQ
Zhu
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D047311:Luteolin / Q000494:pharmacology; D028321:Plant Preparations / Q000494:pharmacology*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000378:metabolism*; D013025:Glycine max / Q000737:chemistry; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D007529:Isoflavones; D028321:Plant Preparations; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C065753:isoflavanone; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D003474:Curcumin; D047311:Luteolin