Network Pharmacology and Experimental Validation Reveal Ganodermanontriol Modulates Pneumonia via TNF/NF‑κB/MAPKs Signaling Pathway
Description
Ganoderma lucidum (Leyss. ex Fr.) Karst has been traditionally used in Chinese medicine for its therapeutic effects, particularly in treating respiratory conditions such as cough and asthma. As a dual-purpose medicinal and edible substance, Lingzhi is widely recognized for promoting health. However, its potential in managing pneumonia remains largely unexplored, requiring further investigation. This study aimed to investigate the therapeutic effects of G. lucidum on pneumonia and to elucidate the underlying mechanisms of action, focusing on the role of its active compounds in modulating inflammatory pathways. Network pharmacology, bioinformatics, molecular docking, and in vivo validation were used. High-performance liquid chromatography and liquid chromatography–mass spectrometry identified eight triterpenoids in G. lucidum, with ganodermanontriol predominating. Molecular docking predicted interactions between compounds and target proteins, while in vivo studies on pneumonia model rats evaluated ganodermanontriol's efficacy. The HPLC and LC–MS analyses identified eight triterpenoids within the ethanol extract of G. lucidum, with ganodermanontriol being the predominant compound. Network pharmacology and molecular docking studies highlighted core genes, including TNF, EGFR, ESR1, HIF1A, HSP90AA1, and SRC, which were significantly involved in the regulation of inflammatory pathways. In vivo studies demonstrated that ganodermanontriol treatment alleviated pulmonary pathological changes in pneumonia model rats by suppressing the release of inflammatory mediators. Mechanistic studies revealed that ganodermanontriol downregulated TNF-α and inhibited the NF-κB/MAPKs signaling pathways. Ganodermanontriol shows promising potential as an anti-inflammatory agent for pneumonia by targeting the TNF/NF-κB/MAPKs signaling pathway, offering a novel therapeutic strategy.