基于网络药理学探索银丹解毒颗粒治疗甲型流感的机制OA

Influenza belongs to the categories of"seasonal epidemic cold"and"epidemic disease"in traditional Chinese medicine theory.Yindan Jiedu Granules(YDJD)is a proven effective traditional Chinese medicine compound for treating pestilence.This study aimed to comprehensively utilize network pharmacology and molecular docking techniques to predict its potential targets and signaling pathways in treating influenza A,and to investigate its mechanisms through in vivo pharmacodynamic experiments.First,the active components of YDJD and its targets were screened using the Traditional Chinese Medicine Systems Pharmacology(TC-MSP)database and the Swiss Target Prediction database respectively,identifying 99 active compounds and 612 drug targets.Simul-taneously,2 366 influenza A-related targets were obtained from the GeneCards and Online Mendelian Inheritance in Man(OMIM)databases,and an intersection analysis yielded 218 potential targets for YDJD in treating influenza A.Using Cytoscape software,di-osmetin,baicalein,norwogonin and acacetin were identified as key active components of YDJD.A protein-protein interaction(PPI)network was constructed via the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)platform,identifying Signal Transducer and Activator of Transcription 3(STAT3),Interleukin-6(IL-6)and Tumor Necrosis Factor(TNF)as key target proteins.Molecular docking results showed strong binding affinity between the key active components and the key target proteins.Gene On-tology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses indicated that YDJD may regulate signaling pathways such as Phosphatidylinositol 3-Kinase-Protein Kinase(PI3K-Akt),TNF and Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells(NF-κB)to mediate apoptosis and inflammatory responses.In vivo experiments were conducted using an H1N1 FM1 strain-induced viral pneumonia model and a PR8 strain-induced lethal model in mice.In the viral pneumonia model,both high and medium doses of YDJD significantly reduced the lung index and viral load in mice(P<0.05).All doses of YDJD significantly inhibited the release of Tumor Necrosis Factor-Alpha(TNF-α),Interferon-Gamma(IFN-γ)and IL-6(P<0.01).High and medium doses of YDJD notably improved lung tissue pathological damage(P<0.01 or P<0.05).In the lethal model,all doses of YDJD significantly reduced mortality(with survival protection rates ranging from 22.22%to 55.56%)and extended sur-vival time(with life extension rates ranging from 27.92%to 51.95%).The results suggested that YDJD may exert therapeutic effects against influenza A by synergistically acting on key protein targets such as IL-6,TNF and STAT3 through its key active components,thereby inhibiting viral replication,alleviating inflammatory responses,improving lung tissue damage and ultimately ameliorating the outcomes of H1N1 influenza virus infection.