基于网络药理学和分子对接研究黄芩汤抗细菌感染的作用机制

Network Pharmacology and Molecular Docking Analyses on Huangqin-Tang Decoction in the Treatment of Bacterial Infection

摘要: 目的：探讨黄芩汤治疗细菌感染的潜在机制及药效物质。方法：通过中药系统药理学数据库与分析平台(TCMSP)和GeneCards数据库获得黄芩汤抗细菌感染的活性成分及基因集。运用STRING数据库进行GO及KEGG通路富集分析，并利用Cytoscape V3.8.3软件构建活性成分–靶点、靶点–靶点相互作用(PPI)以及成分–靶点–通路(C-T-P)网络图。采用AutoDock vina对核心成分和关键靶点进行分子对接，最后借助体外抑菌实验，验证核心成分的抑菌活性。结果：共筛选出黄芩汤抗细菌感染的43个潜在靶点和11个活性成分。网络分析表明，槲皮素、山柰酚、汉黄芩素和β-胡萝卜素可能作用于TNF、CASP3、IL6和JUN 4个核心靶点，并通过Toll-like receptor、NOD-like receptor、NF-kappa B和RIG-I-like receptor signaling pathway等通路发挥抗细菌感染的作用。分子对接结果显示关键靶点与4个核心成分具有较高的亲和力。体外抑菌实验验证槲皮素、山柰酚、汉黄芩素和β-胡萝卜素有较好的抑菌活性。结论：网络药理学方法整合分子对接技术和体外抑菌实验研究，表明黄芩汤治疗细菌感染具有多成分、多靶点和多通路的特点，本文揭示了其药效物质和作用机制，为开发治疗细菌感染的新型联合药物提供了途径。

Abstract: Objective: To explore the potential mechanism and pharmacodynamic substances of Huangqin-Tang decoction in the treatment of bacterial infection. Methods: A target gene set and ac-tive compounds of Huangqin-Tang decoction against bacterial infection were obtained using the Traditional Chinese Medicine Systems Pharmacology database (TCMSP) and GeneCards databases. STRING database was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The compounds-targets network, compounds-targets-pathways net-work (C-T-P) and proteins-proteins interaction (PPI) network were constructed using Cytoscape 3.8.3 software. Molecular docking was performed to visualize the patterns of interactions between the core compounds and key target. Bacteriostatic experiment in vitro was performed to verify the antibacterial activity of core compounds screened. Result: 43 potential targets and 11 active com-pounds of Huangqin-Tang decoction in treatment of bacterial infection were screened. Network analysis indicated that quercetin, kaempferol, wogonin, and beta-carotene may act on 4 core tar-gets, which were TNF, JUN, IL6 and CASP3, and Toll-like Receptor, NOD-like receptor, NF-kappa B, and RIG-I-like receptor signaling pathway and other pathways played a role in anti-bacterial infec-tion. The molecular docking result showed that the key targets had high binding affinity with four core compounds of Huangqin-Tang decoction. In vitro bacteriostatic experimental verified that quercetin, kaempferol had good anti-inflammatory effect. Conclusion: The network pharmacological strategy integrates molecular docking and bacteriostatic experiment in vitro to reveal the thera-peutic effect and potential mechanism of Huangqin-Tang decoction on bacterial infection, which could provide the way to develop new combination medicines for bacterial infection.