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.

Centre de Biologie Structurale INSERM CNRS Université de Montpellier Montpellier France

College of Marine Life Sciences Ocean University of China Qingdao Shandong China

Department of Biological and Environmental Engineering Cornell University Ithaca NY USA

Department of Cell Biology and Genetics Faculty of Science Palacký University Olomouc Czech Republic

Department of Chemistry University of Toronto Toronto ON Canada

Department of Chemistry York University Toronto ON Canada

Department of Earth and Environmental Sciences University of Milano Bicocca Milan Italy

Department of Molecular Genetics University of Toronto Toronto ON Canada

Department of Molecular Pharmacology; Department of Genetics; Department of Medicine Albert Einstein College of Medicine Bronx NY USA

Department of Pharmaceutical Sciences University of Maryland School of Pharmacy Baltimore MD USA

Donnelly Centre for Cellular and Biomolecular Research University of Toronto Toronto ON Canada

Institut de Recherche en Cancérologie de Montpellier Montpellier France

School of Pharmacy Lanzhou University Lanzhou Gansu People's Republic of China

School of the Environment University of Toronto Toronto ON Canada

State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau Macau People's Republic of China

Erratum In

Nat Commun. 2025 Mar 3;16(1):2133. doi: 10.1038/s41467-025-57509-y. PubMed

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