[关键词]
[摘要]
目的 运用网络药理学方法和分子对接技术预测三七治疗腰椎间盘突出症的潜在靶点及作用机制。方法 在TCMSP数据库筛选三七有效活性成分及作用靶点,构建三七“活性成分–靶点”网络。在GeneCards、OMIM数据库检索腰椎间盘突出症相关靶点,取药物与疾病交集靶点,利用String数据库构建蛋白互作(PPI)网络,通过Cytoscape 3.8.2软件构建“成分–靶点–疾病”网络图,并使用R软件进行GO富集分析和KEGG信号通路富集分析。MOE软件对有效成分与潜在靶点作分子对接验证。结果 共筛选三七治疗腰椎间盘突出症的有效活性成分8个、有效药物靶点33个,其中前列腺素内过氧化物合酶、半胱氨酸蛋白酶-3、基质金属蛋白酶9、细胞趋化因子2等靶点基因可能起着关键作用。GO富集分析选取43个条目,主要包括对脂多糖的反应、对细菌来源分子的反应等生物过程;膜筏、膜微区等细胞组分;内肽酶活性、细胞因子受体结合等分子功能。KEGG通路富集分析获得了涉及炎症、细胞凋亡、代谢、免疫、肿瘤等102个条目,其中IL-17信号通路起着关键作用。分子对接结果表明三七主要有效活性成分与核心靶点有较强的结合能力。结论 三七通过多途径、多靶点发挥治疗腰椎间盘突出症的作用。
[Key word]
[Abstract]
Objective To predict the potential target and mechanism of Notoginseng Radix in treatment of lumbar disc herniation by network pharmacology and molecular docking technique. Methods The active components and targets of Notoginseng Radix were screened from TCMSP database, and "active component-target" network of Notoginseng Radix was constructed. The targets related to lumbar disc herniation were retrieved from GeneCards and OMIM databases, and the intersection targets of drugs and diseases were selected. Protein interaction network (PPI) was constructed using String database, the "component-target-disease" network map was constructed by Cytoscape 3.8.2 software, and GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed by R software. MOE software was used to verify the molecular docking between active ingredients and potential targets. Results A total of 8 active components and 33 effective drug targets of Notoginseng Radix were screened for the treatment of lumbar disc herniation. Among them, prostaglandin endoperoxidase synthase, cysteine proteinase-3, matrix metalloproteinase 9, cell chemokine 2, and other target genes may play key roles. Forty-three items were selected for GO enrichment analysis, which mainly included biological processes such as reaction to lipopolysaccharide and reaction to bacteria derived molecules. Membrane raft, membrane microarea and other cell components. Internal peptidase activity, cytokine receptor binding and other molecular functions. KEGG pathway enrichment analysis obtained 102 items related to inflammation, apoptosis, metabolism, immunity and tumor, among which IL-17 signaling pathway played a key role. The molecular docking results showed that the main active components of Notoginseng Radix had strong binding ability to the core target. Conclusion Notoginseng Radix can play a role in treating lumbar disc herniation through multiple ways and multiple targets.
[中图分类号]
R285
[基金项目]
湖南省中医药管理局项目(2021018);湖南省自然科学基金资助项目(2022JJ60076);长沙市科技计划项目(kh2201063)