Pregnane-X-receptor (PXR) is involved in inflammatory bowel disease (IBD). Patchouli alcohol (PA) has anti-inflammatory effects; however, the mechanisms of PA on IBD remain largely unknown.The aim of the present study was to investigate the anti-inflammatory effect of PA that primarily focused on crosstalk between PA-mediated PXR activation and NF-κB inhibition.We evaluated the anti-inflammatory effect of PA with respect to PXR/NF-κB signalling using in vitro and in vivo models. In vitro, the identified PA as PXR agonist was evaluated by hPXR transactivation assays and assessing CYP3A4 expression and activity. NF-κB inhibition were analysed based on NF-κB Luciferase assays, NF-κB-mediated pro-inflammatory genes expression and NF-κB nuclear translocation after activating PXR by PA. In vivo, colonic mPXR and NF-κB signalling were analysed to assess PA-mediated the protective effect against dextran sulphate sodium (DSS)-induced colitis. Furthermore, pharmacological inhibition of PXR was further evaluated the protection of PA against DSS-induced colitis.PA induced CYP3A4 expression and activity via an hPXR-dependent mechanism. PA-mediated PXR activation attenuated inflammation by inhibiting NF-κB activity and nuclear translocation. The anti-inflammatory effect of PA on NF-κB was abolished by PXR knockdown. PA prevented DSS-induced inflammation by regulating PXR/NF-κB signalling, whereas pharmacological PXR inhibition abated PA-mediated suppressive effects on NF-κB inflammation signalling.PA activates PXR signalling and suppresses NF-κB signalling, consequently causing ameliorating inflammation. Results highlight the importance of PXR-NF-κB crosstalk in colitis and suggest a novel therapeutic reagent.
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