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Article Publish Status: FREE
Abstract Title:

Activation of PXR by alantolactone ameliorates DSS-induced experimental colitis via suppressing NF-κB signaling pathway.

Abstract Source:

Sci Rep. 2019 11 12 ;9(1):16636. Epub 2019 Nov 12. PMID: 31719637

Abstract Author(s):

Yijing Ren, Bei Yue, Gaiyan Ren, Zhilun Yu, Xiaoping Luo, Aning Sun, Jingjing Zhang, Mengqing Han, Zhengtao Wang, Wei Dou

Article Affiliation:

Yijing Ren

Abstract:

Alantolactone (ALA) is a sesquiterpene lactone with potent anti-inflammatory activity. However, the effect of ALA on intestinal inflammation remains largely unknown. The present study demonstrated that ALA significantly ameliorated the clinical symptoms of dextran sulfate sodium (DSS)-induced mice colitis as determined by body weight loss, diarrhea, colon shortening, inflammatory infiltration and histological injury. In mice exposed to DSS, ALA treatment significantly lowered pro-inflammatory mediators, including nuclear factor-kappa B (NF-κB) activation. In vitro, ALA inhibited NF-κB nuclear translocation and dose-dependently activated human/mouse pregnane X receptor (PXR), a key regulator gene in inflammatory bowel disease (IBD) pathogenesis. However, the pocket occluding mutants of the ligand-binding domain (LBD) of hPXR, abrogated ALA-mediated activation of the receptor. Overexpression of hPXR inhibited NF-κB-reporter activity and in this setting, ALA further enhanced the hPXR-mediated inhibition of NF-κB-reporter activity. Furthermore, silencing hPXR gene demonstrated the necessity for hPXR in downregulation of NF-κB activation by ALA. Finally, molecular docking studies confirmed the binding affinity between hPXR-LBD and ALA. Collectively, the current study indicates a beneficial effect of ALA on experimental IBD possibly via PXR-mediated suppression of the NF-κB inflammatory signaling.

Study Type : Animal Study

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