An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice
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 f...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56624-0 |
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| author | Xiaojuan Wang Guohui Zhang Zhiwei Bian Vimanda Chow Marina Grimaldi Coralie Carivenc Savannah Sirounian Hao Li Lucia Sladekova Stefano Mott 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 |
| author_facet | Xiaojuan Wang Guohui Zhang Zhiwei Bian Vimanda Chow Marina Grimaldi Coralie Carivenc Savannah Sirounian Hao Li Lucia Sladekova Stefano Mott 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 |
| author_sort | Xiaojuan Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b452a5b5640d4bd5b1ad4bf235fe4379 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b452a5b5640d4bd5b1ad4bf235fe43792025-02-09T12:45:56ZengNature PortfolioNature Communications2041-17232025-02-0116111910.1038/s41467-025-56624-0An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in miceXiaojuan Wang0Guohui Zhang1Zhiwei Bian2Vimanda Chow3Marina Grimaldi4Coralie Carivenc5Savannah Sirounian6Hao Li7Lucia Sladekova8Stefano Mott9Yulia Luperi10Yufeng Gong11Cait Costello12Linhao Li13Matthew Jachimowicz14Miao Guo15Shian Hu16Derek Wilson17Patrick Balaguer18William Bourguet19Sridhar Mani20Laura Bonati21Hui Peng22John March23Hongbing Wang24Shengpeng Wang25Henry M. Krause26Jiabao Liu27School of Pharmacy, Lanzhou UniversityState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauSchool of Pharmacy, Lanzhou UniversityDepartment of Chemistry, York UniversityInstitut de Recherche en Cancérologie de Montpellier (IRCM), Université Montpellier, Institut régional du Cancer de Montpellier (ICM)Centre de Biologie Structurale, INSERM, CNRS, Université de MontpellierCentre de Biologie Structurale, INSERM, CNRS, Université de MontpellierDepartment of Molecular Pharmacology; Department of Genetics; Department of Medicine, Albert Einstein College of MedicineDepartment of Molecular Pharmacology; Department of Genetics; Department of Medicine, Albert Einstein College of MedicineDepartment of Earth and Environmental Sciences, University of Milano-BicoccaDepartment of Earth and Environmental Sciences, University of Milano-BicoccaDepartment of Chemistry, University of TorontoDepartment of Biological and Environmental Engineering, Cornell UniversityDepartment of Pharmaceutical Sciences, University of Maryland School of PharmacyDonnelly Centre for Cellular and Biomolecular Research, University of TorontoState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauSchool of Pharmacy, Lanzhou UniversityDepartment of Chemistry, York UniversityInstitut de Recherche en Cancérologie de Montpellier (IRCM), Université Montpellier, Institut régional du Cancer de Montpellier (ICM)Centre de Biologie Structurale, INSERM, CNRS, Université de MontpellierDepartment of Molecular Pharmacology; Department of Genetics; Department of Medicine, Albert Einstein College of MedicineDepartment of Earth and Environmental Sciences, University of Milano-BicoccaDepartment of Chemistry, University of TorontoDepartment of Biological and Environmental Engineering, Cornell UniversityDepartment of Pharmaceutical Sciences, University of Maryland School of PharmacyState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauDonnelly Centre for Cellular and Biomolecular Research, University of TorontoDonnelly Centre for Cellular and Biomolecular Research, University of TorontoAbstract 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.https://doi.org/10.1038/s41467-025-56624-0 |
| spellingShingle | Xiaojuan Wang Guohui Zhang Zhiwei Bian Vimanda Chow Marina Grimaldi Coralie Carivenc Savannah Sirounian Hao Li Lucia Sladekova Stefano Mott 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 An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice Nature Communications |
| title | An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice |
| title_full | An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice |
| title_fullStr | An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice |
| title_full_unstemmed | An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice |
| title_short | An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice |
| title_sort | abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor pxr in mice |
| url | https://doi.org/10.1038/s41467-025-56624-0 |
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