Nature Communications (Feb 2025)
An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice
- Xiaojuan Wang,
- Guohui Zhang,
- Zhiwei Bian,
- Vimanda Chow,
- Marina Grimaldi,
- Coralie Carivenc,
- Savannah Sirounian,
- Hao Li,
- Lucia Sladekova,
- Stefano Motta,
- Yulia Luperi,
- Yufeng Gong,
- Cait Costello,
- Linhao Li,
- Matthew Jachimowicz,
- Miao Guo,
- Shian Hu,
- Derek Wilson,
- Patrick Balaguer,
- William Bourguet,
- Sridhar Mani,
- Laura Bonati,
- Hui Peng,
- John March,
- Hongbing Wang,
- Shengpeng Wang,
- Henry M. Krause,
- Jiabao Liu
Affiliations
- Xiaojuan Wang
- School of Pharmacy, Lanzhou University
- Guohui Zhang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau
- Zhiwei Bian
- School of Pharmacy, Lanzhou University
- Vimanda Chow
- Department of Chemistry, York University
- Marina Grimaldi
- Institut de Recherche en Cancérologie de Montpellier (IRCM), Université Montpellier, Institut régional du Cancer de Montpellier (ICM)
- Coralie Carivenc
- Centre de Biologie Structurale, INSERM, CNRS, Université de Montpellier
- Savannah Sirounian
- Centre de Biologie Structurale, INSERM, CNRS, Université de Montpellier
- Hao Li
- Department of Molecular Pharmacology; Department of Genetics; Department of Medicine, Albert Einstein College of Medicine
- Lucia Sladekova
- Department of Molecular Pharmacology; Department of Genetics; Department of Medicine, Albert Einstein College of Medicine
- Stefano Motta
- Department of Earth and Environmental Sciences, University of Milano-Bicocca
- Yulia Luperi
- Department of Earth and Environmental Sciences, University of Milano-Bicocca
- Yufeng Gong
- Department of Chemistry, University of Toronto
- Cait Costello
- Department of Biological and Environmental Engineering, Cornell University
- Linhao Li
- Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy
- Matthew Jachimowicz
- Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
- Miao Guo
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau
- Shian Hu
- School of Pharmacy, Lanzhou University
- Derek Wilson
- Department of Chemistry, York University
- Patrick Balaguer
- Institut de Recherche en Cancérologie de Montpellier (IRCM), Université Montpellier, Institut régional du Cancer de Montpellier (ICM)
- William Bourguet
- Centre de Biologie Structurale, INSERM, CNRS, Université de Montpellier
- Sridhar Mani
- Department of Molecular Pharmacology; Department of Genetics; Department of Medicine, Albert Einstein College of Medicine
- Laura Bonati
- Department of Earth and Environmental Sciences, University of Milano-Bicocca
- Hui Peng
- Department of Chemistry, University of Toronto
- John March
- Department of Biological and Environmental Engineering, Cornell University
- Hongbing Wang
- Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy
- Shengpeng Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau
- Henry M. Krause
- Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
- Jiabao Liu
- Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
- DOI
- https://doi.org/10.1038/s41467-025-56624-0
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 19
Abstract
Abstract 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.
