目的 基于网络药理学和分子对接探讨右归丸治疗多发性硬化(multiple sclerosis,MS)的物质基础及作用机制.方法 运用TCMSP数据库筛选右归丸中附子、肉桂、熟地黄、枸杞子、山茱萸、山药、杜仲、菟丝子、当归的活性成分及靶标,通过检索文献及BATMAN-TCM数据库获取鹿角胶活性成分及靶标;运用 GeneCards、OMIM、DrugBank、TTD 数据库筛选 MS 疾病靶标;运用Cytoscape 软件构建右归丸—药物活性成分—靶标、右归丸药物活性成分—交集靶标以及潜在靶标间互作网络图;对潜在靶标进行基因本体分析(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析.结果 右归丸中共获得 1281 个有效活性成分,得到91 个右归丸治疗MS的潜在靶标,这些靶标主要涉及对神经元凋亡过程的负调控、炎症反应等生物学过程,并主要富集在白细胞介素-17(interleukin-17,IL-17)信号通路、肿瘤坏死因子(tumor necrosis factor,TNF)信号通路以及低氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路上.对主要活性成分β-谷甾醇、豆甾醇及核心靶点丝/苏氨酸蛋白激酶(serine/threonine-protein kinase,AKT1)、半胱氨酸天冬氨酸蛋白酶-3(cysteinyl aspartate specific proteinase-3,Caspase-3)、TP53 结合蛋白进行分子对接验证,对接得分显示结合活性较好.结论 右归丸防治MS的作用可能是通过多个化合物作用于多个分子靶点,其分子机制主要是抑制炎症反应,调控IL-17、TNF和HIF-1 等信号通路.
Mechanism analysis on Yougui Pills in the treatment of multiple sclerosis based on network pharmacology and molecular docking
Objective To investigate the material basis and mechanism of Yougui Pills in the treatment of multiple sclerosis(MS)based on network pharmacology and molecular docking.Methods The active ingredients and targets of aconite,cinnamon,rehmannia,wolfberry,dogwood,yam,eucommia,dodder and angelica in Yougui Pills were screened using TCMSP database.The active ingredients and targets of antler gum were obtained by searching literature and BATMAN-TCM database.GeneCards,OMIM,DrugBank,and TTD databases were used to screen MS disease targets.Cytoscape software was used to construct the interaction network diagram between Yougui Pills-active ingredients-targets,Yougui Pills active ingredients-intersection targets and potential targets.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed for the potential targets.Results A total of 1281 active ingredients were obtained from Yougui Pills,and 91 potential targets for the treatment of MS with Yougui Pills were obtained.These targets were mainly involved in the negative regulation of neuronal apoptosis,inflammatory response and other biological processes,and were mainly enriched in interleukin 17(IL-17)signaling pathway,tumor necrosis factor(TNF)signaling pathway and hypoxia inducible factor-1(HIF-1)signaling pathway.The main active ingredients β-sitosterol,stigasterol and core targets AKT1,Caspase-3 and TP53 were verified by molecular docking,and docking scores showed good binding activity.Conclusion The therapeutic effect of Yougui pills in preventing and treating MS is likely mediated through the actions of multiple compounds on various molecular targets.The primary molecular mechanism involves inhibiting inflammatory responses and regulating signaling pathways such as IL-17,TNF and HIF-1.
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