基于网络药理学考察逍遥丸对认知障碍可能作用机制

Study on the action mechanism of xiaoyao pills in the treatment of cognitive impairment based on network pharmacology

目的建立逍遥丸治疗认知障碍的"活性成分-靶标-作用机制"网络,并预测其作用机制。方法采用网络药理学研究方法,应用GeneCards和OMIM在线数据库筛选疾病靶基因;应用TCMSP在线数据库筛选逍遥丸活性成分作用靶标,在Uniprot数据库获取靶标蛋白的基因名并用Venn工具获取药物-疾病交集基因。利用STRING在线数据库构建蛋白相互作用网络,后于Cytoscape 3.6.1软件获取可视化结果,建立药物-靶点-疾病网络,并借助其BiNGO插件进行交集基因的基因本体论(GO)分析,使用DAVID在线数据库对获取的基因进行KEGG通路富集分析,探讨其靶标可能具有的生物学功能及通路。结果从逍遥丸中筛选出163个化合物,涉及治疗认知障碍的100个靶标,网络分析结果表明,逍遥丸可能是基于调控生物过程,调节细胞增殖、凋亡,调节细胞信号传输、代谢等过程发挥治疗认知障碍作用,AGE/RAGE信号通路、PI3K/Akt信号通路、内分泌抵抗信号通路、肿瘤坏死因子信号通路、细胞凋亡信号通路和甲状腺激素信号通路是其可能的主要作用通路。结论逍遥丸可能通过作用于APP、EGFR、ESR1、RELA、FOS、NCOA1、CCND1、MAPK8、IL6、PRKCA、CASP8、APOB、AR、CASP3、CYP1A1、RB1、ERBB2、MDM2、MYC、VEGFA、CHRM2、GSK3B、IKBKB、PPARG、BCL2、HIF1A、IGFBP3、NOS3、PGR、ADRA1A等多个靶点,影响AGE/RAGE信号通路、PI3K/Akt信号通路、内分泌抵抗信号通路、肿瘤坏死因子信号通路、细胞凋亡信号通路和甲状腺激素信号通路等多个通路发挥治疗认知障碍的作用。

Objective To establish the"active components-targets-disease"network of Xiaoyao Pills for the treatment of cognitive impairment(CI)and further predict its mechanism of action.Methods The network pharmacology research method was used to filter the targets of CI by GeneCards and OMIM online database.Using the TCMSP online database to filter the active ingredient targets of Xiaoyao Pills searched the gene symbol of the target protein in the Uniprot database,and obtained the drug-disease intersection genes through the Venn tool.Constructing a protein interaction network in the STRING online database obtained visual effects in the Cytoscape 3.6.1 software and built a drug-target-disease network,which BiNGO plugin was used to do Gene ontology(GO)analysis of intersection genes,and then performed KEGG pathway enrichment analysis by the DAVID online database to explore the possible biological functions and pathways of potential targets.Results A total of 163 compounds was screened out from Xiaoyao Pills and involved 100 targets for the treatment of CI.The results of network analysis indicated that Xiaoyao Pills'treatment of CI might be based on regulating biological processes,cell proliferation,apoptosis,cell signal transmission and metabolism,among which main pathways possibly included AGE/RAGE signaling pathway,PI3K/Akt signaling pathway,endocrine resistance signaling pathway,TNF signaling pathway,apoptosis signaling pathway and thyroid hormone signaling pathway.Conclusion Xiaoyao Pills might treat CI by acting on APP,EGFR,ESR1,RELA,FOS,NCOA1,CCND1,MAPK8,IL6,PRKCA,CASP8,APOB,AR,CASP3,CYP1A1,RB1,ERBB2,MDM2,MYC,VEGFA,CHRM2,GSK3B,IKBKB,PPARG,BCL2,HIF1A,IGFBP3,NOS3,PGR,ADRA1A and many other targets,affecting the AGE/RAGE signaling pathway,PI3K/Akt signaling pathway,endocrine resistance signaling pathway,TNF signaling pathway,apoptosis signaling pathway,thyroid hormone signaling pathway and so on.