Analysis of flavonoids regulating the expression of UGT1A1 via xenobiotic receptors in intestinal epithelial cells.

UDP-glucuronosyltransferase (UGT) 1A1 is one of the major metabolic enzymes for the detoxification of harmful xenobiotics in intestines, and its expression is regulated by transcription factors like the aryl hydrocarbon receptor (AhR) and the pregnane X receptor (PXR). A screening assay using real-time PCR showed that baicalein and 3-hydroxyflavone induced human UGT1A1 mRNA expression in LS180 cells. Experimental results confirmed that these flavonoids increased UGT1A protein expression as well as its enzymatic activity. The results indicated that baicalein and 3-hydroxyflavone increased the transcriptional activity of UGT1A1 via AhR and PXR, respectively. Observation via immunofluorescence microscopy suggested that baicalein and 3-hydroxyflavone further induced nuclear translocation of AhR and PXR, respectively. In addition, direct interaction between baicalein and AhR or 3-hydroxyflavone and PXR were observed using the quartz crystal microbalance method. These results elucidate the molecular mechanism of flavonoid-induced UGT1A1 gene expression via xenobiotic receptors in the intestines.