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Rus-GXF, a ruscogenin glycoside, binds to the ADP-binding domain of JAK1 to prevent inflammation and barrier damage in acute lung injury
by
Tian, Meng-Liang
, Chen, Xing-Fu
, Wu, Chun
, Liu, Long
, Zhao, Jia-He
, Si, Kai-Shuai
, Wang, Nan-Nan
, Yin, Zhong-Qiong
, Li, Li-Xia
, Zhou, Xun
, Li, Mei-Qi
, Duan, Xu
, Gu, Yi
, Zou, Yuan-Feng
in
acute lung injury
/ Allosteric properties
/ Bronchus
/ Cell culture
/ Chemokines
/ Cytokine storm
/ Cytokines
/ Epithelial cells
/ Experiments
/ Glycosides
/ Immunohistochemistry
/ Inflammation
/ JAK1/STAT3
/ Janus kinase
/ kinase inhibitor
/ Laboratory animals
/ Lavage
/ Ligands
/ Lungs
/ Macrophages
/ Medical research
/ Metabolites
/ Molecular dynamics
/ molecule
/ Original Research
/ Phosphorylation
/ Quality control
/ Signal transduction
/ Stat3 protein
/ Traditional Chinese medicine
/ Transcriptomes
/ Transcriptomics
/ Tumor necrosis factor-TNF
2026
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Rus-GXF, a ruscogenin glycoside, binds to the ADP-binding domain of JAK1 to prevent inflammation and barrier damage in acute lung injury
by
Tian, Meng-Liang
, Chen, Xing-Fu
, Wu, Chun
, Liu, Long
, Zhao, Jia-He
, Si, Kai-Shuai
, Wang, Nan-Nan
, Yin, Zhong-Qiong
, Li, Li-Xia
, Zhou, Xun
, Li, Mei-Qi
, Duan, Xu
, Gu, Yi
, Zou, Yuan-Feng
in
acute lung injury
/ Allosteric properties
/ Bronchus
/ Cell culture
/ Chemokines
/ Cytokine storm
/ Cytokines
/ Epithelial cells
/ Experiments
/ Glycosides
/ Immunohistochemistry
/ Inflammation
/ JAK1/STAT3
/ Janus kinase
/ kinase inhibitor
/ Laboratory animals
/ Lavage
/ Ligands
/ Lungs
/ Macrophages
/ Medical research
/ Metabolites
/ Molecular dynamics
/ molecule
/ Original Research
/ Phosphorylation
/ Quality control
/ Signal transduction
/ Stat3 protein
/ Traditional Chinese medicine
/ Transcriptomes
/ Transcriptomics
/ Tumor necrosis factor-TNF
2026
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Rus-GXF, a ruscogenin glycoside, binds to the ADP-binding domain of JAK1 to prevent inflammation and barrier damage in acute lung injury
by
Tian, Meng-Liang
, Chen, Xing-Fu
, Wu, Chun
, Liu, Long
, Zhao, Jia-He
, Si, Kai-Shuai
, Wang, Nan-Nan
, Yin, Zhong-Qiong
, Li, Li-Xia
, Zhou, Xun
, Li, Mei-Qi
, Duan, Xu
, Gu, Yi
, Zou, Yuan-Feng
in
acute lung injury
/ Allosteric properties
/ Bronchus
/ Cell culture
/ Chemokines
/ Cytokine storm
/ Cytokines
/ Epithelial cells
/ Experiments
/ Glycosides
/ Immunohistochemistry
/ Inflammation
/ JAK1/STAT3
/ Janus kinase
/ kinase inhibitor
/ Laboratory animals
/ Lavage
/ Ligands
/ Lungs
/ Macrophages
/ Medical research
/ Metabolites
/ Molecular dynamics
/ molecule
/ Original Research
/ Phosphorylation
/ Quality control
/ Signal transduction
/ Stat3 protein
/ Traditional Chinese medicine
/ Transcriptomes
/ Transcriptomics
/ Tumor necrosis factor-TNF
2026
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Rus-GXF, a ruscogenin glycoside, binds to the ADP-binding domain of JAK1 to prevent inflammation and barrier damage in acute lung injury
Journal Article
Rus-GXF, a ruscogenin glycoside, binds to the ADP-binding domain of JAK1 to prevent inflammation and barrier damage in acute lung injury
2026
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Overview
Ruscogenin-1-O-[β-D-glucopyranosyl (1→2)][β-D-xylopyranosyl (1→3)] -β-D-fucopyranoside (Rus-GXF) is a ruscogenin glycoside of
(Decaisne) L. H. Bailey, yet its protective effects against acute lung injury-a condition characterized by exacerbated inflammation and barrier damage have not been fully elucidated.
In this study, the preventive and therapeutic effects of Rus-GXF on acute lung injury (ALI) were investigated using transcriptome RNA sequencing, network pharmacology, molecular docking, molecular dynamics simulation and other
and
experiments.
Rus-GXF suppressed inflammatory responses in two key cell types involved in lung injury. In immune cells (RAW264.7), it inhibited the production of pivotal pro-inflammatory mediators and their regulatory genes. Similarly, in pulmonary epithelial cells (BEAS-2B), it reduced the expression of inflammatory signals and concurrently enhanced markers of cellular tight junction proteins. In mice, Rus-GXF alleviated ALI severity, evidenced by decreased lung wet/dry ratio, bronchoalveolar lavage fluid protein content, pro-inflammatory cytokine levels, and histopathological scores. Integrated network pharmacology and transcriptomics indicated that Rus-GXF acts through multi-target mechanisms in ALI. Molecular docking and dynamics simulations revealed that Rus-GXF acts as an allosteric inhibitor of JAK1, thereby preventing its activation and subsequent STAT3 phosphorylation. The inhibitory effect of Rus-GXF on the JAK1/STAT3 signaling pathway was investigated by immunohistochemistry (IHC) and Western blot analysis (WB).
These results demonstrate that Rus-GXF suppresses the macrophage-derived cytokine storm, alleviates inflammation, and improves barrier function. It functions as a JAK1 inhibitor to regulate ALI progression via the JAK1/STAT3 signaling pathway.
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