Objective: To explore the potential effective targets and mechanism of Punica granatum L. against influenza based on network pharmacology and verify them with animal model. Methods: The active components in Punica granatum L. were retrieved by Chinese Medicine System Pharmacology Platform (TCMSP), and active targets were screened. The Cytoscape software was used to construct network of Punica granatum L. for influenza treatment. The targets of influenza A were screened through databases such as TTD and DRUGBANK. STRING database was used to construct the network of influenza A, and the biological function annotation and pathway analysis of key targets were performed. Mice of experimental model were infected with influenza A. The expression of key proteins and inflammatory factors of IL-17 pathway was detected by ELISA and Western blot. The body weight and lung index of mice were detected. Results: There were 7 active components in Punica granatum L. against influenza A and 96 effective targets. Among them, RELA, MAPK1, JUN, HIF1A, ESR1, NFKBIA and TP53 genes may be the core targets. The possible mechanism of action may be related to IL-17 signaling pathway, chemical carcinogenic-receptor activation, phosphatidylinositol 3-kinase pathway, etc. Preliminary animal experiments showed that Punica granatum L. extracts were involved in the regulation of IL-17 pathway to inhibit the expression of inflammatory cytokines IL-6, TNF-α, IL-1β and TRAF6, NF-κB protein (P＜0.05). Conclusion: There are 6 components contained in Punica granatum L. interacting with different targets and pathways to inhibit the expression of proteins of multiple inflammatory cytokines to inhibit influenza A.
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