ReferenceID 1126
Activation of PXR by Alpinetin Contributes to Abrogate Chemically Induced Inflammatory Bowel Disease
Front Pharmacol
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 alpi
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Record Fields
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- Reference Id
- 1126
- Evidence Id
- 17716
- Core Evidence Id
- 17716
- Source Reference Id
- 2228
- Herb2 Reference Id
- HBREF003025
- Subject Paper Key
- HBIN015751_32372959
- Pubmed Id
- 32372959
- Doi
- 10.3389/fphar.2020.00474
- Paper Title
- Activation of PXR by Alpinetin Contributes to Abrogate Chemically Induced Inflammatory Bowel Disease
- Paper Abstract
- 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-alpha-induced NF-kappaB-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-kappaB regulatory mechanism governing alpinetin's anti-inflammatory effects in a murine model of IBD.
- Journal
- Front Pharmacol
- Publish Year
- 2020
- Experiment Subject
- mouse; human; ginger; lipopolysaccharide (lps)-stimulated raw264.7 macrophages; ls174t colorectal cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Inflammatory Bowel Disease; Colitis
- Paper Title Cn
- Paper Title En
- Activation of PXR by Alpinetin Contributes to Abrogate Chemically Induced Inflammatory Bowel Disease
- Bilingual Status
- semi_complete