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

X. Wang, G. Zhang, Z. Bian, V. Chow, M. Grimaldi, C. Carivenc, S. Sirounian, H. Li, L. Sladekova, S. Motta, Y. Luperi, Y. Gong, C. Costello, L. Li, M. Jachimowicz, M. Guo, S. Hu, D. Wilson, P. Balaguer, W. Bourguet, S. Mani, L. Bonati, H. Peng,...

. 2025 ; 16 (1) : 1280. [pub] 20250203

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc25009957

Grant support
RGPIN480432 Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)
PJT-186117 Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
82204227 National Natural Science Foundation of China (National Science Foundation of China)
R01 CA222469 NCI NIH HHS - United States
CRDPJ597036 Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)

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.

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$a Wang, Xiaojuan $u School of Pharmacy, Lanzhou University, Lanzhou, Gansu, People's Republic of China
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$a An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice / $c X. Wang, G. Zhang, Z. Bian, V. Chow, M. Grimaldi, C. Carivenc, S. Sirounian, H. Li, L. Sladekova, S. Motta, Y. Luperi, Y. Gong, C. Costello, L. Li, M. Jachimowicz, M. Guo, S. Hu, D. Wilson, P. Balaguer, W. Bourguet, S. Mani, L. Bonati, H. Peng, J. March, H. Wang, S. Wang, HM. Krause, J. Liu
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$a 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.
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