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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Nature communications
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39900639/ |
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| _version_ | 1868266247447117824 |
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| author | Wang, Xiaojuan Zhang, Guohui Bian, Zhiwei Chow, Vimanda Grimaldi, Marina Carivenc, Coralie Sirounian, Savannah Li, Hao Sladekova, Lucia Motta, Stefano Luperi, Yulia Gong, Yufeng Costello, Cait Li, Linhao Jachimowicz, Matthew Guo, Miao Hu, Shian Wilson, Derek Balaguer, Patrick Bourguet, William Mani, Sridhar Bonati, Laura Peng, Hui March, John Wang, Hongbing Wang, Shengpeng Krause, Henry M Liu, Jiabao |
| author_facet | Wang, Xiaojuan Zhang, Guohui Bian, Zhiwei Chow, Vimanda Grimaldi, Marina Carivenc, Coralie Sirounian, Savannah Li, Hao Sladekova, Lucia Motta, Stefano Luperi, Yulia Gong, Yufeng Costello, Cait Li, Linhao Jachimowicz, Matthew Guo, Miao Hu, Shian Wilson, Derek Balaguer, Patrick Bourguet, William Mani, Sridhar Bonati, Laura Peng, Hui March, John Wang, Hongbing Wang, Shengpeng Krause, Henry M Liu, Jiabao Wang, Xiaojuan Zhang, Guohui Bian, Zhiwei Chow, Vimanda Grimaldi, Marina Carivenc, Coralie Sirounian, Savannah Li, Hao Sladekova, Lucia Motta, Stefano Luperi, Yulia Gong, Yufeng Costello, Cait Li, Linhao Jachimowicz, Matthew Guo, Miao Hu, Shian Wilson, Derek Balaguer, Patrick Bourguet, William Mani, Sridhar Bonati, Laura Peng, Hui March, John Wang, Hongbing Wang, Shengpeng Krause, Henry M Liu, Jiabao |
| collection | PubMed - marine biology |
| contents | An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice. Wang, Xiaojuan Zhang, Guohui Bian, Zhiwei Chow, Vimanda Grimaldi, Marina Carivenc, Coralie Sirounian, Savannah Li, Hao Sladekova, Lucia Motta, Stefano Luperi, Yulia Gong, Yufeng Costello, Cait Li, Linhao Jachimowicz, Matthew Guo, Miao Hu, Shian Wilson, Derek Balaguer, Patrick Bourguet, William Mani, Sridhar Bonati, Laura Peng, Hui March, John Wang, Hongbing Wang, Shengpeng Krause, Henry M Liu, Jiabao Animals Pregnane X Receptor Male Zingiber officinale Mice Furans Humans Mice, Inbred C57BL Colon Anti-Inflammatory Agents Colitis Inflammation 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 | Artículo científico |
| id | pubmed_39900639 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Nature communications |
| record_format | pubmed |
| spellingShingle | An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice. Wang, Xiaojuan Zhang, Guohui Bian, Zhiwei Chow, Vimanda Grimaldi, Marina Carivenc, Coralie Sirounian, Savannah Li, Hao Sladekova, Lucia Motta, Stefano Luperi, Yulia Gong, Yufeng Costello, Cait Li, Linhao Jachimowicz, Matthew Guo, Miao Hu, Shian Wilson, Derek Balaguer, Patrick Bourguet, William Mani, Sridhar Bonati, Laura Peng, Hui March, John Wang, Hongbing Wang, Shengpeng Krause, Henry M Liu, Jiabao Animals Pregnane X Receptor Male Zingiber officinale Mice Furans Humans Mice, Inbred C57BL Colon Anti-Inflammatory Agents Colitis Inflammation An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice. Wang, Xiaojuan Zhang, Guohui Bian, Zhiwei Chow, Vimanda Grimaldi, Marina Carivenc, Coralie Sirounian, Savannah Li, Hao Sladekova, Lucia Motta, Stefano Luperi, Yulia Gong, Yufeng Costello, Cait Li, Linhao Jachimowicz, Matthew Guo, Miao Hu, Shian Wilson, Derek Balaguer, Patrick Bourguet, William Mani, Sridhar Bonati, Laura Peng, Hui March, John Wang, Hongbing Wang, Shengpeng Krause, Henry M Liu, Jiabao Animals Pregnane X Receptor Male Zingiber officinale Mice Furans Humans Mice, Inbred C57BL Colon Anti-Inflammatory Agents Colitis Inflammation 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. |
| title | An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice. |
| topic | Animals Pregnane X Receptor Male Zingiber officinale Mice Furans Humans Mice, Inbred C57BL Colon Anti-Inflammatory Agents Colitis Inflammation |
| url | https://pubmed.ncbi.nlm.nih.gov/39900639/ |