PT  - JOURNAL ARTICLE
AU  - Wang, Laiyou
AU  - Li, Feng
AU  - Lu, Jie
AU  - Li, Guodong
AU  - Li, Dan
AU  - Zhong, Xiao-bo
AU  - Guo, Grace L.
AU  - Ma, Xiaochao
TI  - The Chinese Herbal Medicine <em>Sophora flavescens</em> Activates Pregnane X Receptor
AID  - 10.1124/dmd.110.035253
DP  - 2010 Dec 01
TA  - Drug Metabolism and Disposition
PG  - 2226--2231
VI  - 38
IP  - 12
4099  - http://dmd.aspetjournals.org/content/38/12/2226.short
4100  - http://dmd.aspetjournals.org/content/38/12/2226.full
SO  - Drug Metab Dispos2010 Dec 01; 38
AB  - Sophora flavescens (SF) is an herbal medicine widely used for the treatment of viral hepatitis, cancer, viral myocarditis, gastrointestinal hemorrhage, and skin diseases. It was recently reported that SF up-regulates CYP3A expression. The mechanism of SF-induced CYP3A expression is unknown. In the current study, we tested the hypothesis that SF-induced CYP3A expression is mediated by the activation of pregnane X receptor (PXR). We used two cell lines, DPX2 and HepaRG, to investigate the role of PXR in SF-induced CYP3A expression. The DPX2 cell line is derived from HepG2 cells with the stable transfection of human PXR and a luciferase reporter gene linked with a human PXR response element identified in the CYP3A4 gene promoter. In DPX2 cells, SF activated PXR in a concentration-dependent manner. We used a metabolomic approach to identify the chemical constituents in SF, which were further analyzed for their effect on PXR activation and CYP3A regulation. One chemical in SF, N-methylcytisine, was identified as an individual chemical that activated PXR. HepaRG is a highly differentiated hepatoma cell line that mimics human hepatocytes. In HepaRG cells, N-methylcytisine significantly induced CYP3A4 expression, and this induction was suppressed by the PXR antagonist sulforaphane. These results suggest that SF induces CYP3A expression via the activation of PXR.