Mechanisms underlying the mitigating action of Maxing Shigan Decoction in acute lung injury caused by influenza virus based on UPLC-HRMS analysis and network pharmacology

In the rat serum, 242 bioactive components were identified using UPLC-HRMS. Moreover, 56 ingredients, including glycyrrhizin, amygdalin, and ephedrine, were analyzed using network pharmacology, revealing 338 ALI-related targets and 99 core proteins in the protein-protein interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted for core targets, and molecular docking confirmed the binding affinity of the main identified targets with their respective blood-absorbed components. Validation results demonstrated that MXSGD significantly ameliorated lung injury, mitigated lung congestion and inflammation, lowered viral load in mouse lung tissue, promoted macrophage polarization, and downregulated the expression of the PI3K/AKT pathway in IAV-infected mice. Overall, this study revealed the mechanisms and active ingredients underlying the therapeutic effects, highlighting of MXSGD its potential in treating IAV-induced ALI and regulating the polarization of macrophages.