TY - JOUR T1 - Identification of <em>Ginkgo biloba</em> as a Novel Activator of Pregnane X Receptor JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 2270 LP - 2276 DO - 10.1124/dmd.108.023499 VL - 36 IS - 11 AU - Eugene Y. H. Yeung AU - Tatsuya Sueyoshi AU - Masahiko Negishi AU - Thomas K. H. Chang Y1 - 2008/11/01 UR - http://dmd.aspetjournals.org/content/36/11/2270.abstract N2 - Pregnane X receptor (PXR; NR1I2) is a ligand-activated transcription factor that plays a role not only in drug metabolism and transport but also in various other biological processes. Ginkgo biloba is a herbal medicine commonly used to manage memory impairment. Treatment of primary cultures of rat hepatocytes with G. biloba extract increases the mRNA expression of CYP3A23, which is a target gene for rat PXR. The present study was conducted to test the hypothesis that G. biloba extract activates PXR. Treatment of mouse PXR (mPXR) or human PXR (hPXR)-transfected HepG2 cells with G. biloba extract at 200 μg/ml increased mPXR and hPXR activation by 3.2- and 9.5-fold, respectively. Dose-response analysis showed a log-linear increase in hPXR activation by the extract over the range of 200 to 800 μg/ml. To determine whether G. biloba extract induces hPXR target gene expression, cultured LS180 human colon adenocarcinoma cells were treated for 72 h with the extract. G. biloba extract at 200, 400, and 800 μg/ml increased CYP3A4 mRNA expression by 1.7-, 2.4-, and 2.5-fold, respectively. The same concentrations of the extract increased CYP3A5 (1.3-3.6-fold) and P-glycoprotein (ABCB) 1 (2.7-6.4-fold) mRNA expression. At concentrations (5 and 10 μM) that did not down-regulate PXR gene expression and were not cytotoxic, l-sulforaphane (an hPXR antagonist) decreased CYP3A4, CYP3A5, and ABCB1 gene expression in cells treated with G. biloba extract. In summary, G. biloba extract activated mPXR and hPXR in a cell-based reporter gene assay and induced CYP3A4, CYP3A5, and ABCB1 gene expression in hPXR-expressing LS180 cells. The American Society for Pharmacology and Experimental Therapeutics ER -