Oleanolic acid (OA) is an ingredient found in some Traditional Chinese Medicine remedies for treating liver ailments. Bile acid biosynthesis and catabolism are in part controlled in the liver by transcription factor farnesoid X receptor (FXR). It was hypothesized that OA may act through FXR to mediate some of its benefi cial health effects. In this study, it was found that OA bound to the ligand binding domain (LBD) of FXR and blocked its ability to interact with coactivator SRC-3. OA also dose-dependently suppressed the activity of FXR-LBD induced by its endogenous ligand chenodoxycholic acid (CDCA). Consistently, OA partially blocked the ability of CDCA to induce a FXR target gene bile salt export protein (BSEP). On the other hand, OA did not affect the expression of another FXR target gene organic solute transporter (OST-b). Intriguingly, OA modestly enhanced the expression of a third FXR target gene short heterodimer partner (SHP). This evidence
collectively suggested that OA acts as a gene selective modulator of FXR. Copyright ” 2009 John Wiley & Sons, Ltd.