TY - JOUR T1 - Ginsenosides Regulate PXR/NF-<em>κ</em>B Signaling and Attenuate Dextran Sulfate Sodium–Induced Colitis JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1181 LP - 1189 DO - 10.1124/dmd.115.063800 VL - 43 IS - 8 AU - Jun Zhang AU - Lijuan Cao AU - Hong Wang AU - Xuefang Cheng AU - Lin Wang AU - Lin Zhu AU - Tingting Yan AU - Yang Xie AU - Yuzheng Wu AU - Min Zhao AU - Sijing Ma AU - Mengqiu Wu AU - Guangji Wang AU - Haiping Hao Y1 - 2015/08/01 UR - http://dmd.aspetjournals.org/content/43/8/1181.abstract N2 - Pregnane X receptor (PXR) activation exhibits anti-inflammatory effects via repressing nuclear factor-κB (NF-κB); however, its overactivation may disrupt homeostasis of various enzymes and transporters. Here we found that ginsenosides restore PXR/NF-κB signaling in inflamed conditions without disrupting PXR function in normal conditions. The effects and mechanisms of ginsenosides in regulating PXR/NF-κB signals were determined both in vitro and in vivo. Ginsenosides significantly inhibited NF-κB activation and restored the expression of PXR target genes in tumor necrosis factor-α–stimulated LS174T cells. Despite not being PXR agonists, ginsenosides repressed NF-κB activation in a PXR-dependent manner. Ginsenosides significantly increased the physical association between PXR and the NF-κB p65 subunit and thereby decreased the nuclear translocation of p65. Ginsenoside Rb1 and compound K (CK) were major bioactive compounds in the regulating PXR/NF-κB signaling. Consistently, ginsenosides significantly attenuated dextran sulfate sodium–induced experimental colitis, which was associated with restored PXR/NF-κB signaling. This study indicates that ginsenosides may elicit anti-inflammatory effects via targeting PXR/NF-κB interaction without disrupting PXR function in healthy conditions. Ginsenoside Rb1 and CK may serve as leading compounds in the discovery of new drugs that target PXR/NF-κB interaction in therapy for inflammatory bowel disease. ER -