基于网络药理学探讨人参调控铁死亡抗阿尔茨海默病的潜在作用机制

Potential mechanism of Ginseng Radix et Rhizoma for treatment of Alzheimer’s disease by regulating ferroptosis based on network pharmacology

目的采用网络药理学方法探讨人参抗阿尔茨海默病的可能靶标及作用机制。方法利用TCMSP数据库获取人参活性成分及其所对应的靶标。通过GeneCards数据库获取阿尔茨海默病的治疗靶标。利用Venn在线工具获得人参活性成分和阿尔茨海默病的共同作用靶点。运用Cytoscape软件构建人参、活性成分、靶标间相互作用网络关系图,并使用CytoHubba插件获得核心靶点以及核心子网络。应用DAVID数据库进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。检索FerrDb数据库,获得调控铁死亡的基因并进行分析,最终综合探析人参活性成分、阿尔茨海默病、铁死亡3者关系并作出预测。结果从人参中筛选出具有作用靶点的16个有效活性成分,预测得到以HMOX1、NOS2、PTGS2、IFNG、MAPK8、JUN和RELA 7个人参调控铁死亡抗阿尔茨海默病的可能作用靶标,介导HIF-1、TNF、T细胞受体、Toll样受体、神经营养因子、cAMP、MAPK、NOD样受体等信号通路调控铁死亡途径,从而对抗阿尔茨海默病的发生及进展。结论利用网络药理学探讨了人参抗阿尔茨海默病的多成分、多靶点、多通路的作用特点,并挖掘出人参活性成分调控铁死亡抗阿尔茨海默病的可能靶点及信号转导机制。

Objective The possible target and mechanism of Ginseng Radix et Rhizoma against Alzheimer’s disease were investigated by network pharmacology method.Methods The active ingredients of Ginseng Radix et Rhizoma and their corresponding targets were obtained by using TCMSP database.Therapeutic targets for Alzheimer’s disease were obtained from GeneCards database.The co-action targets of Ginseng Radix et Rhizoma active ingredients and Alzheimer’s disease were obtained using Venn online tool.Cytoscape software was used to construct the network diagram of interaction between Ginseng Radix et Rhizoma,active ingredient and target,and CytoHubba plug-in was used to obtain the core target and core subnetwork.DAVID database was used for gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.FerrDb database was searched to obtain and analyze the genes regulating ferroptosis.Finally,the data of Ginseng Radix et Rhizoma active ingredients,Alzheimer’s disease and ferroptosis were comprehensively analyzed and predicted.Results Sixteen active components were screened from Ginseng Radix et Rhizoma,and seven possible targets of Ginseng Radix et Rhizoma regulating ferroptosis and anti-Alzheimer’s disease were predicted,including HMOX1,NOS2,PTGS2,IFNG,MAPK8,JUN,and RELA.Ferroptosis pathway is regulated by mediating HIF-1,TNF,T cell receptor,Toll-like receptor,neurotrophic factor,cAMP,MAPK,NOD-like receptor,and other signaling pathways,thus combating the occurrence and progression of Alzheimer’s disease.Conclusion The multi-component,multi-target and multi-pathway action characteristics of Ginseng Radix et Rhizoma against Alzheimer’s disease were explored by using network pharmacology,and the possible targets and signal transduction mechanism of Ginseng Radix et Rhizoma active ingredients regulating ferroptosis against Alzheimer’s disease were explored.