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An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice

Author

Listed:
  • Xiaojuan Wang

    (Lanzhou University)

  • Guohui Zhang

    (University of Macau)

  • Zhiwei Bian

    (Lanzhou University)

  • Vimanda Chow

    (York University)

  • Marina Grimaldi

    (Institut régional du Cancer de Montpellier (ICM))

  • Coralie Carivenc

    (Université de Montpellier)

  • Savannah Sirounian

    (Université de Montpellier)

  • Hao Li

    (Albert Einstein College of Medicine)

  • Lucia Sladekova

    (Albert Einstein College of Medicine
    Palacký University)

  • Stefano Motta

    (University of Milano-Bicocca)

  • Yulia Luperi

    (University of Milano-Bicocca)

  • Yufeng Gong

    (University of Toronto
    Ocean University of China)

  • Cait Costello

    (Cornell University)

  • Linhao Li

    (University of Maryland School of Pharmacy)

  • Matthew Jachimowicz

    (University of Toronto
    University of Toronto)

  • Miao Guo

    (University of Macau)

  • Shian Hu

    (Lanzhou University)

  • Derek Wilson

    (York University)

  • Patrick Balaguer

    (Institut régional du Cancer de Montpellier (ICM))

  • William Bourguet

    (Université de Montpellier)

  • Sridhar Mani

    (Albert Einstein College of Medicine)

  • Laura Bonati

    (University of Milano-Bicocca)

  • Hui Peng

    (University of Toronto
    University of Toronto)

  • John March

    (Cornell University)

  • Hongbing Wang

    (University of Maryland School of Pharmacy)

  • Shengpeng Wang

    (University of Macau)

  • Henry M. Krause

    (University of Toronto
    University of Toronto)

  • Jiabao Liu

    (University of Toronto)

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.

Suggested Citation

  • 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 Coste, 2025. "An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56624-0
    DOI: 10.1038/s41467-025-56624-0
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    References listed on IDEAS

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