基于网络药理学及分子对接技术分析远志治疗原发性失眠作用机制

Analysis of Mechanism of Polygalae Radix in Treating Primary Insomnia Based on Network Pharmacology and Molecular Docking Technology

目的:基于网络药理学及分子对接技术分析远志治疗原发性失眠(PI)的作用机制。方法:通过Herb、Batman-TCM数据库筛选远志的化合物,用Swiss Target Prediction、SEA及Batman-TCM数据库行主要活性成分潜在靶点筛选,同时在Gene Cards、NCBI基因、TTD数据库筛选疾病相关靶点。将远志的主要活性成分靶点与疾病靶点输入Venny2.1行交集处理,筛选两者的共同靶点,运用Cytoscape3.8.0软件构建“药物-成分-疾病-靶点”PPI网络并行拓扑分析。使用RStudio4.0.3软件行基因本体(GO)功能富集与京都基因和基因组百科全书(KEGG)通路富集分析,使用Discovery Studio软件将远志主要活性成分与疾病核心靶点进行分子对接。结果:筛选出远志中含有金丝桃苷、α-菠甾醇、芦丁、槲皮素等9种主要活性成分,261个药物潜在作用靶点,与2 600个PI相关疾病靶点取交集后获得87个共有靶点。拓扑分析筛选到白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、人环磷酸腺苷反应元件结合蛋白1 (CREB1)、血管内皮生长因子A (VEGFA)、丝裂原活化蛋白激酶3(MAPK3)等36个关键靶点。GO功能富集分析得到BP条目1 302项、MF相关条目101项、CC相关条目63项;KEGG通路富集分析筛选到神经活性配体-受体相互作用、γ-氨基丁酸(GABA)、磷脂酰肌醇3-激酶/蛋白激酶-B (PI3K-Akt)、环磷酸腺苷(cAMP)、TNF等79条信号通路;分子对接显示远志主要活性成分与疾病核心靶点亲和力均良好。结论:远志能够通过多成分、多靶点、多通路的协同作用影响机体的神经代谢、氧化应激及炎症反应,从而发挥治疗PI的作用。

Objective: To analyze the mechanism of Polygalae Radix in treating primary insomnia(PI) based on network pharmacology and molecular docking technology. Methods:The compounds of Polygalae Radixwere screened through Herb and Batman-TCM databases;potential targets of main active components were screened by Swiss Target Prediction,SEA and Batman-TCM databases,and diseaserelated targets were screened in Gene Cards,NCBI Genes,and TTD databases. The targets of main active components and disease targets of Polygalae Radix were input into Venny 2.1 for intersection processing,and their common targets were screened out,and Cytoscape 3.8.0 software was used to build a“drugcomponent-disease-target” PPI network and the topological data analysis was carried out. RStudio4.0.3software was used to perform gene ontology(GO) function enrichment analysis;the Kyoto Encyclopedia of Genes and Genomes(KEGG) was used for pathway enrichment analysis;Discovery Studio software was used to perform molecular docking between the main active components of Polygalae Radix and the core targets of the disease. Results: It was found that, in Radix Polygalae, there were nine main active components including Hypericin,α-Spinosterol,rutin and quercetin,261 potential drug targets,and 87common targets after the intersection with 2 600 PI-related disease targets. A total of 36 core targets,including interleukin-6(IL-6), tumor necrosis factor(TNF), cAMP responsive element-binding protein 1(CREB1),vascular endothelial growth factor A(VEGFA),and mitogen-activated protein kinase 3(MAPK3) were screened by topological data analysis. By the GO function enrichment analysis,1 302 BP entries,101 MF related entries, and 63 CC related entries were obtained. By the KEGG pathway enrichment analysis,79 signal pathways were screened, including neuroactive ligand-receptor interaction pathway, γ-aminobutyric acid(GABA) pathway, phosphatidylinositol-3-kinase/protein kinase-B(PI3K-Akt) pathway,cyclic adenosine monophosphate(cAMP) and TNF;molecular docking showed that the main active components of Polygalae Radix had a good affinity with core disease targets. Conclusion:Polygalae Radix can affect the nervous metabolism,oxidative stress and inflammatory reactions of the body through the synergistic effect of multiple components,multiple targets and multiple pathways,thus playing a role in the treatment of PI.