Activation of PXR by Alpinetin Contributes to Abrogate Chemically Induced Inflammatory Bowel Disease

Zhilun Yu, Bei Yue, Lili Ding, Xiaoping Luo, Yijing Ren, Jingjing Zhang, Sridhar Mani, Zhengtao Wang, Wei Dou

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Alpinetin is a naturally occurring flavonoid from the ginger plants. We previously reported the identification of alpinetin as a ligand of human pregnane X receptor (hPXR). The current study investigated the role of alpinetin as a putative PXR activator in ameliorating chemically induced inflammatory bowel disease (IBD). We found that oral administration of alpinetin significantly alleviated the severity of dextran sulfate sodium (DSS)-induced colitis in mice by decreasing the inflammatory infiltration, the levels of the pro-inflammatory mediators, and the PXR target genes in the colon. In vitro, alpinetin blocked the nuclear translocation of p-p65 in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Further, alpinetin significantly upregulated PXR target genes and inhibited TNF-α-induced NF-κB-luciferase activity in LS174T colorectal cells; however, this regulatory effects were lost when cellular PXR gene was knocked down. In PXR transactivation assays, alpinetin increased both mouse and human PXR transactivation in a dose-dependent manner. Ligand occluding mutants, S247W/C284W and S247W/C284W/S208W, in hPXR-reporter assays, abrogated alpinetin-induced hPXR transactivation. Finally, alpinetin bound to the hPXR-ligand-binding domain (LBD) was confirmed by competitive ligand binding assay. The current study significantly extends prior observations by validating a PXR/NF-κB regulatory mechanism governing alpinetin’s anti-inflammatory effects in a murine model of IBD.

Original languageEnglish (US)
Article number474
JournalFrontiers in Pharmacology
StatePublished - Apr 21 2020


  • alpinetin
  • inflammatory bowel disease
  • nuclear factor-kappa B
  • pregnane X receptor
  • xenobiotics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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