Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium–Induced Colitis
| Autor: | Haiping Hao, Jun Zhang, Hong Wang, Yang Xie, Xuefang Cheng, Min Zhao, Sijing Ma, Lin Zhu, Mengqiu Wu, Yuzheng Wu, Guangji Wang, Lijuan Cao, Lin Wang, Tingting Yan |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Receptors Steroid Ginsenosides Pharmaceutical Science Pharmacology digestive system Cell Line Mice In vivo Animals Receptor Pregnane X receptor Tumor Necrosis Factor-alpha Chemistry Anti-Inflammatory Agents Non-Steroidal Dextran Sulfate NF-kappa B Pregnane X Receptor Transcription Factor RelA Transporter Colitis digestive system diseases In vitro Mice Inbred C57BL Neuroprotective Agents Cell culture Tumor necrosis factor alpha Homeostasis Signal Transduction |
| Zdroj: | Drug Metabolism and Disposition. 43:1181-1189 |
| ISSN: | 1521-009X 0090-9556 |
| DOI: | 10.1124/dmd.115.063800 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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