基于网络药理学和分子对接探讨复方双花口服液治疗流感的作用机制

Mechanism of Compound Shuanghua oral liquid in the treatment of influenza based on network pharmacology and molecular docking

目的:运用网络药理学方法和分子对接技术探究复方双花口服液治疗流感可能的作用机制。方法:通过文献查找复方双花口服液活性成分,根据数据平台对复方双花口服液的活性成分的作用靶点进行预测,构建化合物-靶点网络。将复方双花口服液活性成分靶点与流感疾病靶点取交集,得到关键靶点,构建药物-活性成分-关键靶点-疾病网络。通过对共有核心靶点进行蛋白质相互作用分析,分析蛋白相互作用(PPI)中度中心度(DC)、中间性中心性(BC)、紧密性中心性(CC)、特征向量中心性(EC)、网络中心性(NC)和局部平均连通性(LAC)参数,筛选核心靶基因;选取的复方双花口服液主要活性成分与流感病毒神经氨酸酶靶点进行分子对接。结果:获得复方双花口服液对应靶点的活性成分80个,预测作用靶点616个,流感相关基因2 574个,复方双花口服液治疗流感的关键靶点243个,PPI分析筛选出23个关键核心靶点,包括原癌基因酪氨酸蛋白激酶Src(SRC)、酪氨酸蛋白激酶JAK1(JAK1)等;富集分析显示复方双花口服液和流感的共同生物学过程与炎症反应、细胞增殖及凋亡等相关,作用的主要通路为肿瘤坏死因子信号通路、白细胞介素-17信号通路、凋亡信号通路、Toll样受体信号通路、C型凝集素受体信号通路等。分子对接的结果显示主要活性成分与流感病毒神经氨酸酶具有较好结合活性。结论:复方双花口服液可能主要通过抑制神经氨酸酶活性、炎症反应及凋亡相关因子和通路抗流感,减轻流感引起的炎症反应,从而达到治疗流感的目的。

Objective: Network pharmacology and molecular docking technology were used to explore the possible mechanism of Compound Shuanghua oral liquid in the treatment of influenza. Methods: The active ingredients of the compound Shuanghua oral liquid were searched through the literature, and the target points of the active ingredients were predicted based on the data platform, after which a compound-target network was constructed. The intersection of the active ingredient targets of the compound Shuanghua oral liquid and the influenza disease targets were taken to obtain the key targets to construct a drug-active ingredient-key target-disease network. Protein interaction analysis was conducted through shared core targets. The protein interaction core(PPI) moderate centrality(DC), intermediate centrality(BC), compact centrality(CC), eigenvector centrality(EC), network centrality(NC) and local average connectivity(LAC) parameters were analyzed to screen the core target genes. The selected main active components of the Compound Shuanghua oral liquid are molecularly docked with the influenza virus neuraminidase target. Results: Totally 80 active ingredients were obtained corresponding to the targets of Compound Shuanghua oral liquid;616 action targets, 2 574 influenza-related genes, 243 key targets of Compound Shuanghua oral liquid were predicted in the treatment of influenza, and 23 key core targets were screened from protein interaction core(PPI) analysis, including proto-oncogene tyrosine protein kinase Src(SRC), tyrosine protein kinase JAK1(JAK1), etc. Enrichment analysis showed the common biological process of compound Shuanghua oral liquid and influenza, which is related to inflammation, cell proliferation and apoptosis. The main pathways of action are tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, and C-type lectin receptor signaling Access, etc. The results of molecular docking show that the main active ingredients have good binding activity with influenza virus neuraminidase. Conclusion: The mechanism of action for Compound Shuanghua oral liquid may mainly be inhibiting neuraminidase activity, inflammatory response and apoptosis related factors and pathways, acting against influenza, reducing the inflammatory response caused by influenza, so as to achieve the purpose of treating influenza.