Influenza virus is one of the most common infectious pathogens that could cause high morbidity and mortality in humans. However, the occurrence of drug resistance and serious complications extremely complicated the clinic therapy. 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. But the therapeutic effects of this herbal medicine had not been expounded clearly. In this study, a network pharmacology approach was employed to investigate the protective mechanism of total flavonoids from M. scabra (MSTF) against influenza A virus- (IAV-) induced acute lung damage and inflammation. The active compounds of MSTF were analyzed by LC-MS/MS and then evaluated according to their oral bioavailability and drug-likeness index. The potential targets of each active compound in MSTF were identified by using PharmMapper Server, whereas the potential genes involved in IAV infection were obtained from GeneGards. The results showed that luteoloside, apigenin, kaempherol, luteolin, mosloflavone I, and mosloflavone II were the main bioactive compounds found in MSTF. Primarily, 23 genes were identified as the targets of those five active compounds, which contributed to the inactivation of chemical carcinogenesis ROS, lipid and atherosclerosis, MAPK signaling pathway, pathways in cancer, PI3K-AKT signaling pathway, proteoglycans in cancer, and viral carcinogenesis. Finally, the animal experiments validated that MSTF improved IAV-induced acute lung inflammation via inhibiting MAPK, PI3K-AKT, and oxidant stress pathways. Therefore, our study demonstrated the potential inhibition of MSTF on viral pneumonia in mice and provided a strategy to characterize the molecular mechanism of traditional Chinese medicine by a combinative method using network pharmacology and experimental validation.

The lower respiratory tract infection, induced by influenza virus, coronaviruses, and respiratory syncytial virus, remains a serious threat to human health that can cause a global pandemic. 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. It indicated that MSTL enhanced the function of alveolar macrophages and improved IAV-induced lung injury in mice.