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Objective <p>Sepsis is a severe condition characterized by life-threatening organ dysfunction resulting from an excessive host response to infection. Among the affected organs, the lungs are particularly susceptible during the progression of sepsis. Tussilagone (TS), a sesquiterpenoid compound derived from the flowers of <i>Tussilago farfara</i>, has been explored for its potential therapeutic effects on sepsis-induced lung injury. This study used both in vitro and in vivo experimental approaches, complemented by network pharmacology analyses, to verify the mechanisms and molecular targets underlying the effects of TS.</p> Methods <p>TS was administered to mice with sepsis-induced lung injury and to lung epithelial cells stimulated with lipopolysaccharide (LPS) to assess its therapeutic potential. Inflammatory factor levels in mouse serum, lung tissue, and cells were assessed. Western blot analysis was used to determine the expression of NF-κB p65 and MyD88 in lung tissues. Potential molecular TS targets were identified, with receptor-interacting serine/threonine-protein kinase 1 (<i>RIPK1</i>) selected for further investigation using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Additionally, the study explored if TS exerts its protective effects against lung injury in septic mice through targeted regulation of <i>RIPK1</i>.</p> Results <p>TS inhibited the NF-κB p65 and MyD88 signaling pathways, reducing the release of inflammatory factors and a mitigation of lung injury severity in LPS-induced MLE12 cells and CLP-induced septic mice. Overexpression of RIPK1 protein resulted in elevated expression levels of NF-κB p65 and MyD88, whereas treatment with TS significantly reduced these levels. Similarly, the use of a RIPK1 protein inhibitor to suppress <i>RIPK1</i> expression also decreased the expression of NF-κB p65 and MyD88, further supporting the role of <i>RIPK1</i> in the mechanism of TS-mediated lung protection.</p> Conclusion <p>TS demonstrates a protective effect against sepsis-induced acute lung injury (ALI) by inhibiting the expression of <i>RIPK1</i>. These findings indicate that TS can potentially be a therapeutic agent for the treatment of ALI.</p>

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Tussilagone mitigates sepsis-induced acute lung injury in mice by suppressing RIPK1 expression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月21日

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  • Jie Gu,
  • Yachen Cai,
  • Jiangwen Yin,
  • Mengjie Zhang,
  • Jun Chen,
  • Hongjun Miao

摘要

Objective

Sepsis is a severe condition characterized by life-threatening organ dysfunction resulting from an excessive host response to infection. Among the affected organs, the lungs are particularly susceptible during the progression of sepsis. Tussilagone (TS), a sesquiterpenoid compound derived from the flowers of Tussilago farfara, has been explored for its potential therapeutic effects on sepsis-induced lung injury. This study used both in vitro and in vivo experimental approaches, complemented by network pharmacology analyses, to verify the mechanisms and molecular targets underlying the effects of TS.

Methods

TS was administered to mice with sepsis-induced lung injury and to lung epithelial cells stimulated with lipopolysaccharide (LPS) to assess its therapeutic potential. Inflammatory factor levels in mouse serum, lung tissue, and cells were assessed. Western blot analysis was used to determine the expression of NF-κB p65 and MyD88 in lung tissues. Potential molecular TS targets were identified, with receptor-interacting serine/threonine-protein kinase 1 (RIPK1) selected for further investigation using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Additionally, the study explored if TS exerts its protective effects against lung injury in septic mice through targeted regulation of RIPK1.

Results

TS inhibited the NF-κB p65 and MyD88 signaling pathways, reducing the release of inflammatory factors and a mitigation of lung injury severity in LPS-induced MLE12 cells and CLP-induced septic mice. Overexpression of RIPK1 protein resulted in elevated expression levels of NF-κB p65 and MyD88, whereas treatment with TS significantly reduced these levels. Similarly, the use of a RIPK1 protein inhibitor to suppress RIPK1 expression also decreased the expression of NF-κB p65 and MyD88, further supporting the role of RIPK1 in the mechanism of TS-mediated lung protection.

Conclusion

TS demonstrates a protective effect against sepsis-induced acute lung injury (ALI) by inhibiting the expression of RIPK1. These findings indicate that TS can potentially be a therapeutic agent for the treatment of ALI.