The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases.

• MeSH
• antiflogistika farmakologie   chemie   MeSH
• furany farmakologie   MeSH
• kolitida farmakoterapie   chemicky indukované   metabolismus   patologie   MeSH
• kolon účinky léků   patologie   metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• pregnanový X receptor * metabolismus   genetika   MeSH
• zánět farmakoterapie   metabolismus   MeSH
• zázvor lékařský * chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH