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<p>Acute lung injury (ALI), a severe respiratory syndrome driven by dysregulated inflammatory cascades, urgently requires novel therapeutic strategies. The activation of the MyD88 (Myeloid differentiation factor 88)-mediated TLR (Toll-like receptor) inflammatory signaling pathway plays a crucial role in the pathophysiology of ALI, while minimally involving interferon-mediated responses. Targeting MyD88 offers a promising approach for ALI drug development. Here, we employed surface plasmon resonance (SPR) and in vitro anti-inflammatory screening methods to evaluate the interaction of candidate drugs with MyD88 and their anti-inflammatory activity. This was followed by anti-inflammatory verification in lipopolysaccharide (LPS)-induced ALI mice. Our findings reveal that Fisetin, a flavonoid derived from <i>Cotinus coggygria</i>, exhibited the strongest MyD88-binding affinity and suppressed MyD88 homodimerization, thereby blocking downstream NF-κB and MAPK activation. In LPS-challenged mice, Fisetin significantly reduced pulmonary inflammatory levels, decreased lung wet/dry ratio, and attenuated neutrophil infiltration. In conclusion, Fisetin emerges as a novel MyD88 inhibitor that disrupts TLR-driven inflammatory amplification, positioning it as a phytotherapeutic candidate for ALI.</p> Graphical Abstract <p></p>

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Fisetin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Targeting Myeloid Differentiation Factor 88

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月13日

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  • Zhongqian Jin,
  • Xin Liu,
  • Zhuohui Xie,
  • Yuting Xie,
  • Kangmin Xu,
  • Shengnan Zhao,
  • Zengxian Zhou,
  • Chenghao Qian,
  • Yuxiao Jiang,
  • Fenfen Lin,
  • Yue Liu,
  • Ruping Chen,
  • Gaozhi Chen,
  • Yunjie Wang

摘要

Acute lung injury (ALI), a severe respiratory syndrome driven by dysregulated inflammatory cascades, urgently requires novel therapeutic strategies. The activation of the MyD88 (Myeloid differentiation factor 88)-mediated TLR (Toll-like receptor) inflammatory signaling pathway plays a crucial role in the pathophysiology of ALI, while minimally involving interferon-mediated responses. Targeting MyD88 offers a promising approach for ALI drug development. Here, we employed surface plasmon resonance (SPR) and in vitro anti-inflammatory screening methods to evaluate the interaction of candidate drugs with MyD88 and their anti-inflammatory activity. This was followed by anti-inflammatory verification in lipopolysaccharide (LPS)-induced ALI mice. Our findings reveal that Fisetin, a flavonoid derived from Cotinus coggygria, exhibited the strongest MyD88-binding affinity and suppressed MyD88 homodimerization, thereby blocking downstream NF-κB and MAPK activation. In LPS-challenged mice, Fisetin significantly reduced pulmonary inflammatory levels, decreased lung wet/dry ratio, and attenuated neutrophil infiltration. In conclusion, Fisetin emerges as a novel MyD88 inhibitor that disrupts TLR-driven inflammatory amplification, positioning it as a phytotherapeutic candidate for ALI.

Graphical Abstract