ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Rus-GXF, a ruscogenin glycoside, binds to the ADP-binding domain of JAK1 to 1 prevent inflammation and barrier damage in acute lung injury
Long Liu 1
Xu Duan 1
Mei-Qi Li 2
Yi Gu 1
Jia-He Zhao 1
Kai-Shuai Si 1
Nan-Nan Wang 1
Xing-Fu Chen 2
Zhongqiong Yin 1
Li-Xia Li 1
Xun Zhou 1
Chun Wu 3
Mengliang Tian 2
Yuan-Feng Zou 1
1. Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Si chuan, China
2. Sichuan Agricultural University College of Agronomy, Chengdu, China
3. Sichuan Agricultural University, Ya'an, China
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Abstract
Background: Ruscogenin-1-O-[β-D-glucopyranosyl (1→2)][β-D-xylopyranosyl (1→3)] 23 -β-D-fucopyranoside (Rus-GXF) is a ruscogenin glycoside of Liriope muscari 24 (Decaisne) L. H. Bailey, yet its protective effects against acute lung injury — a 25 condition characterized by exacerbated inflammation and barrier damage have not been 26 fully elucidated. 27 Methods: In this study, the preventive and therapeutic effects of Rus-GXF on acute 28 lung injury (ALI) were investigated using transcriptome RNA sequencing, network 29 pharmacology, molecular docking, molecular dynamics simulation and other in vitro 30 and in vivo experiments. 31 Results: Rus-GXF suppressed inflammatory responses in two key cell types involved in 32 lung injury. In immune cells (RAW264.7), it inhibited the production of pivotal 33 pro-inflammatory mediators and their regulatory genes. Similarly, in pulmonary 34 epithelial cells (BEAS-2B), it reduced the expression of inflammatory signals and 35 concurrently enhanced markers of cellular tight junction proteins. In mice, Rus-GXF 36 alleviated ALI severity, evidenced by decreased lung wet/dry ratio, bronchoalveolar 37 lavage fluid protein content, pro-inflammatory cytokine levels, and histopathological 38 scores. Integrated network pharmacology and transcriptomics indicated that Rus-GXF 39 acts through multi-target mechanisms in ALI. Molecular docking and dynamics 40 simulations revealed that Rus-GXF acts as an allosteric inhibitor of JAK1, thereby 41 preventing its activation and subsequent STAT3 phosphorylation. The inhibitory effect 42 of Rus-GXF on the JAK1/STAT3 signaling pathway was investigated by 43 immunohistochemistry (IHC) and western blot analysis (WB). 44 Conclusion: These results demonstrate that Rus-GXF suppresses the 45 macrophage-derived cytokine storm, alleviates inflammation, and improves barrier 46 function. It functions as a JAK1 inhibitor to regulate ALI progression via the 47 JAK1/STAT3 signaling pathway.
Summary
Keywords
Acute Lung Injury, Inflammation, JAK1/STAT3, kinase inhibitor, molecule
Received
22 October 2025
Accepted
20 February 2026
Copyright
© 2026 Liu, Duan, Li, Gu, Zhao, Si, Wang, Chen, Yin, Li, Zhou, Wu, Tian and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Li-Xia Li; Yuan-Feng Zou
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