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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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    1. Jiabao Liu & Ainaz Malekoltojari & Anjana Asokakumar & Vimanda Chow & Linhao Li & Hao Li & Marina Grimaldi & Nathanlown Dang & Jhenielle Campbell & Holly Barrett & Jianxian Sun & William Navarre & Der, 2024. "Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. James R. Bayrer & Hongtao Wang & Roy Nattiv & Miyuki Suzawa & Hazel S. Escusa & Robert J. Fletterick & Ophir D. Klein & David D. Moore & Holly A. Ingraham, 2018. "LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    3. Vanessa Delfosse & Béatrice Dendele & Tiphaine Huet & Marina Grimaldi & Abdelhay Boulahtouf & Sabine Gerbal-Chaloin & Bertrand Beucher & Dominique Roecklin & Christina Muller & Roger Rahmani & Vincent, 2015. "Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    4. Efren Garcia-Maldonado & Andrew D. Huber & Sergio C. Chai & Stanley Nithianantham & Yongtao Li & Jing Wu & Shyaron Poudel & Darcie J. Miller & Jayaraman Seetharaman & Taosheng Chen, 2024. "Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Mei Lan Chen & Xiangsheng Huang & Hongtao Wang & Courtney Hegner & Yujin Liu & Jinsai Shang & Amber Eliason & Huitian Diao & HaJeung Park & Blake Frey & Guohui Wang & Sarah A. Mosure & Laura A. Solt &, 2021. "CAR directs T cell adaptation to bile acids in the small intestine," Nature, Nature, vol. 593(7857), pages 147-151, May.
    6. Jinhang Zhang & Ya Huang & Hong Li & Pengfei Xu & Qinhui Liu & Yang Sun & Zijing Zhang & Tong Wu & Qin Tang & Qingyi Jia & Yan Xia & Ying Xu & Xiandan Jing & Jiahui Li & Li Mo & Wen Xie & Aijuan Qu & , 2024. "B3galt5 functions as a PXR target gene and regulates obesity and insulin resistance by maintaining intestinal integrity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
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