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<p>Severe burns can cause secondary pulmonary inflammation driven by endotoxin-related inflammatory activation and oxidative stress. Here, we integrated untargeted LC-MS, network pharmacology, transcriptomics, molecular docking, molecular dynamics simulation and target-engagement assays to identify and validate a candidate active constituent from <i>Ganoderma lucidum</i>. LC-MS identified 660 compounds, with terpenoids as a predominant class. Network pharmacology prioritized inflammatory signaling pathways related to PI3K-Akt, MAPK and NF-κB, and integration with RNA-seq identified 92 transcriptomics-supported candidate targets. Ganoderic acid L showed favorable predicted binding to PIK3CA and was selected for experimental validation. In an LPS-induced inflammatory lung injury mouse model, ganoderic acid L alleviated histopathological injury, pulmonary edema and bronchoalveolar lavage fluid protein leakage; reduced TNF-α, IL-6, IL-1β, MPO and MDA levels; and restored SOD and GSH-Px activities. RT-qPCR and western blotting indicated suppression of inflammatory gene expression and modulation of Akt/NF-κB/MAPK signaling. Surface plasmon resonance showed micromolar-level interaction with PI3K, and CETSA provided supportive evidence for potential target engagement. These findings identify ganoderic acid L as a candidate anti-inflammatory triterpenoid for LPS-induced lung injury, while causal PI3K engagement requires further validation.</p>

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Ganoderic acid L attenuates LPS-induced inflammatory lung injury through integrated network pharmacology, transcriptomics and target-engagement analyses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Jian Zhang,
  • Hongtao Xiao,
  • Lei Wang,
  • Xiaoliang Li,
  • Chengde Xia,
  • Haiping Di

摘要

Severe burns can cause secondary pulmonary inflammation driven by endotoxin-related inflammatory activation and oxidative stress. Here, we integrated untargeted LC-MS, network pharmacology, transcriptomics, molecular docking, molecular dynamics simulation and target-engagement assays to identify and validate a candidate active constituent from Ganoderma lucidum. LC-MS identified 660 compounds, with terpenoids as a predominant class. Network pharmacology prioritized inflammatory signaling pathways related to PI3K-Akt, MAPK and NF-κB, and integration with RNA-seq identified 92 transcriptomics-supported candidate targets. Ganoderic acid L showed favorable predicted binding to PIK3CA and was selected for experimental validation. In an LPS-induced inflammatory lung injury mouse model, ganoderic acid L alleviated histopathological injury, pulmonary edema and bronchoalveolar lavage fluid protein leakage; reduced TNF-α, IL-6, IL-1β, MPO and MDA levels; and restored SOD and GSH-Px activities. RT-qPCR and western blotting indicated suppression of inflammatory gene expression and modulation of Akt/NF-κB/MAPK signaling. Surface plasmon resonance showed micromolar-level interaction with PI3K, and CETSA provided supportive evidence for potential target engagement. These findings identify ganoderic acid L as a candidate anti-inflammatory triterpenoid for LPS-induced lung injury, while causal PI3K engagement requires further validation.