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Thus, finding effective chemicals and therapeutic measures to advance the functional restoration of the respiratory tract after infection has been the emphasis of the studies on the subjects. Mosla scabra is a natural medicinal plant used for treating various lung and gastrointestinal diseases, including viral infection, cough, chronic obstructive pulmonary disease, acute gastroenteritis, and diarrhoea. In this study, the antiviral and anti-inflammatory effects of total lignans (MSTL) extracted from the plant were investigated in influenza A virus (IAV)-infected mice and RAW 264.7 macrophages. MSTL could not only protect the macrophages against IAV-induced pyroptosis but also could lighten the lung inflammation induced by IAV in vivo and in vitro. The network pharmacology analysis revealed that differentially expressed genes, mainly involving in EGFR tyrosine kinase inhibitor resistance, endocrine resistance, HIF-1 signaling pathway, C-type lectin receptor signaling pathway, and FOXO signaling pathway, contributed to the IAV-induced alveolar macrophage dysfunction. 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