目的:基于网络药理学和分子对接技术探讨参枝苓口服液治疗阿尔茨海默病(AD)的作用机制。方法:利用中药系统药理学分析平台(TCMSP)和中药分子机制的生物信息学分析工具数据库(BATMAN-TCM)查找与参枝苓口服液中中药相关的化学成分及其作用靶点;通过 DisGeNET数据库获取与 AD 相关的靶标，并进一步筛选得到参枝苓口服液治疗 AD 的潜在作用靶点;利用Cytoscape软件构建成分-靶点相互作用网络，确认可能的关键靶点和关键通路;采用 DAVID数据库对筛选出的潜在作用靶点进行基因本体(GO)功能分析及京都基因与基因组百科全书(KEGG)代谢通路富集分析;通过分子对接预测活性成分与靶蛋白的结合能力。结果:在参枝苓口服液中，共筛选出 34个与 AD相关的潜在活性成分和 56个潜在作用靶点;GO生物功能分析共包含 541条富集结果，主要涉及基因表达的正向调节、同源蛋白结合等;KEGG富集得到 214条代谢通路，主要包括 AD及自噬信号通路等。分子对接结果表示β-谷甾醇、山柰酚、木犀草素与半胱氨酸蛋白酶 3(CASP3)、前列腺素内过氧化物合酶(PTGS2)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、B细胞淋巴瘤/白血病-2(Bcl-2)均可较好结合，可能是参枝苓口服液抗 AD最有效的活性成分。结论:网络药理学及分子对接研究结果揭示了参枝苓口服液治疗 AD的多成分、多靶点、多途径的作用特点，并预测了其可能的活性成分、作用通路和关键靶点，为其药效物质基础和作用机制提供了理论基础。
The Mechanism of Shenzhiling Oral Liquid for Treating Alzheimer's Disease Based on Network Pharmacology and Molecular Docking
Objective:To investigate the mechanism of Shenzhiling oral liquid for treating Alzheimer's disease(AD)based on network pharmacology and molecular docking technology.Methods:The chemical constituents related to traditional Chinese medicine(TCM)in Shenzhiling oral liquid and its action targets were found in Systematic Pharmacology Database and Analysis Platform of TCM(TCMSP)and bioinformatics analysis tool database of TCM molecular mechanism(BATMAN-TCM)database.The targets related to AD were obtained through DisGeNET database,and the potential targets of Shenzhiling oral liquid for the treatment of AD were further screened.A component-target interaction network were contructed using Cytoscape software to identify possible key targets and critical pathways.DAVID database was used for gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of potential targets.Molecular docking was used to predict the binding ability of active ingredients with target proteins.Results:A total of 34 potential active ingredients and 56 potential targets related to AD were screened in Shenzhiling oral liquid.GO biofunctional analysis contained a total of 541 enrichment results,which were mainly related to the positive regulation of gene expression and homologous protein binding,etc.KEGG enrichment yielded 214 metabolic pathways,which were mainly included the signaling pathways of Alzheimer's disease and autophagy signaling pathway.The molecular docking results indicated that β-sitosterol,kaempferol,and luteolin bind well with CASP3,PTGS2,IL6,TNF,and Bcl-2,which may be the most effective active ingredients of Shenzhiling oral liquid against Alzheimer's disease.Conclusion:The results of network pharmacology and molecular docking studies revealed the multi-component,multi-target,and multi-pathway action characteristics of Shenzhiling oral liquid for the treatment of Alzheimer's disease,and predicted its possible active components,action pathways and key targets,which provided theoretical foundations for the material basis of efficacy and mechanism of action.
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