Aspirin’s therapeutic mechanism against diesel particulate matter-induced lung injury revealed by network pharmacology and experimental models

Occupational exposure to diesel particulate matter (DPM) poses significant risks of pulmonary injury, highlighting an urgent need for effective pharmacological intervention. This study aimed to systematically elucidate the protective mechanism of aspirin against DPM-induced lung injury by integrating computational and experimental approaches. Methodologically, network pharmacology utilizing SwissTargetPrediction and GeneCards identified PTGS2 as the core therapeutic target via Venn diagram analysis and topological screening. Molecular docking and dynamics simulations then confirmed the stable binding of aspirin to the PTGS2 catalytic pocket. Biological validation was conducted via colony formation assay and Western blot in A549 cells, which demonstrated aspirin's efficacy in mitigating DPM-induced cytotoxicity and suppressing inflammatory and apoptotic pathways. Furthermore, <i>in vivo</i> studies incorporating HE staining and protein analysis in a mouse model corroborated the protective role of aspirin against DPM-induced alveolar damage and inflammatory infiltration. Collectively, our findings validate PTGS2 as a critical therapeutic target of aspirin against DPM-induced lung injury and highlight the promise of pulmonary-targeted aspirin formulations to enhance therapeutic precision while reducing systemic toxicity. Future efforts should focus on advancing the clinical translation of inhalable aspirin and validating its long-term efficacy in high-risk occupational populations.