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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/