基于网络药理学和分子对接探讨新香冲剂治疗流感的作用机制＊

目的 该研究通过网络药理学和分子对接技术探讨新香冲剂治疗流感的作用机制。方法 首先,基于SymMap、PubChem、FAF-Drugs4、TargetNet等网站工具,筛选新香冲剂中的活性成分,预测其靶点。通过GEO数据库获得人类流感疾病靶点。利用Cytosacpe3.6.0软件构建中药-成分、成分-靶点、药物-疾病蛋白相互作用(Protein-Protein Interaction,PPI)网络,对网络进行拓扑结构分析,筛选出关键化合物和关键靶点。提取核心子网络,利用DAVID6.8在线工具对核心子网络的靶点做基因本体(Gene Ontology,GO)分析和京东基因百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。利用分子对接方法分析关键化合物和关键靶点的相互作用关系。结果 成分-靶点网络分析得到9种重要的活性化合物,关键化合物为芹菜素(Apigenin)。药物、疾病网络的共同靶点基质金属蛋白酶9(Matrix Metalloproteinase-9,MMP9)是关键靶点。GO分析显示核心子网络与抗炎、调节免疫等多个生物学过程相关。KEGG富集分析得到甲型流感疾病通路。分子对接显示,芹菜素与MMP9可通过氢键结合形成稳定的构象。结论 新香冲剂通过抗病毒、抗炎、调节免疫等机制治疗流感,调控宿主细胞MMP9的表达是其发挥作用的途径之一,以上结论有待进一步开展实验验证。

Mechanism of Xinxiang Granule in treating Influenza based on Network Pharmacology and Molecular Docking

Objective This study aimed to explore the mechanism of Xinxiang Granule to treat the influenza based on network pharmacology and molecular docking.Methods By searching SymMap, PubChem, FAF-Drugs4 and TargetNet database, the active ingredients of Xinxiang Granule and targets were acquired. Human influenza targets were obtained through GEO online database. Then the target networks of drug and disease and protein-protein interaction(PPI)were constructed and analyzed by Cytosacape3.6.0 software independently. The hub compound and hub target were screened. The intersection targets network of PPI network of drug and disease was constructed and called core subnetwork. Using DAVID6.8 online tool to analyze the Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the targets in core subnetwork.Result It indicated that nine important compounds were acquired and the hub compound was Apigenin. The common target of drug and disease network is Matrix metalloproteinase 9(MMP9). MMP9 is also a hub target. The GO function analysis implied that targets in core subnetwork were related to anti-inflammation and immunoregulation. Influenza A disease pathway was obtained by KEGG enrichment analysis. Apigenin and MMP9 can form a stable conformation by hydrogen bonding through molecular docking.Conclusion Xinxiang Granule was used to treat influenza through anti-inflammatory function and immune-regulating processes. Regulating the expression of MMP9 in host cells was one of its effective pathways. This conclusion needed further research and experimental verification.