复方苁蓉益智胶囊治疗阿尔茨海默病作用机制的网络药理学研究

Network Pharmacological Study on Mechanism of Compound Congrong Yizhi Capsule in Treatment of Alzheimer’s Disease

目的利用网络药理学技术研究复方苁蓉益智胶囊(CCYC)治疗阿尔茨海默病(AD)的潜在作用机制。方法利用TCMSP、BATMAN-TCM数据库、TCMID数据库、化学专业数据库查找复方苁蓉益智胶囊中5味中药的化学成分并进行活性成分筛选;利用SwissTargetPrediction数据库获取活性成分的作用靶点,搜索GeneCards数据库、OMIM数据库、TTD数据库结合文献查找获取阿尔茨海默病的疾病靶点。取活性成分靶点和阿尔茨海默病疾病靶点的交集,得到复方苁蓉益智胶囊治疗阿尔茨海默病的潜在靶点。利用String数据库构建蛋白质-蛋白质互作网络。采用Metascape平台进行靶点GO富集分析和KEGG富集分析,通过Cytoscape3.7.1软件构建"单味药-关键成分-靶点-通路"网络并进行分析。结果肉苁蓉含有最多的关键成分,荷叶有最多的潜在靶点。APP、MAPK1、MAPK3、ESR2、ESR1、EGFR、DRD2、ACHE可能是复方苁蓉益智胶囊治疗阿尔茨海默病的重要靶点,涉及的主要通路和过程主要包括神经递质受体活性、神经递质水平调控、多巴胺能突触、胆碱能突触等。结论肉苁蓉和荷叶在复方苁蓉益智胶囊复方中占主要地位,复方苁蓉益智胶囊治疗阿尔茨海默病的机制可能是减少Aβ的产生及tau蛋白形成、调节雌激素受体及表皮生长因子受体、调控多巴胺能及胆碱能系统。

Objective To study the potential mechanism of Compound Congrong Yizhi Capsule(CCYC)in the treatment of Alzheimer’s disease(AD)by using network pharmacology.Methods The compounds in five traditional Chinese medicines of CCYC were searched from TCMSP,BATMAN-TCM,TCMID and Chemical Database,and then the active compounds were screened.The SwissTargetPrediction database was used to obtain the targets of the active compounds.The targets of AD were searched from GeneCards,OMIM and TTD database besides published literature.Potential targets of CCYC to treat AD were obtained by taking the intersection of active compound targets and AD disease targets.A protein-protein interaction(PPI)network was built by the String database.The gene ontology(GO)enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment were carried out on the Metascape platform,and the drugs-key compounds-targets-pathways network was constructed and analyzed through Cytoscape 3.7.1 software.Results Cistanche deserticola had the most key compounds and lotus leaf had the most potential targets.APP,MAPK1,MAPK3,ESR2,ESR1,EGFR,DRD2 and AChE may be the important targets of CCYC in the treatment of AD.The pathways and processes involved mainly include neurotransmitter receptor activity,neurotransmitter level regulation,dopaminergic synapse,cholinergic synapse,etc.Conclusion Cistanche deserticola and lotus leaf play a vital important role in CCYC.The mechanism of CCYC in the treatment of AD may be related to reduce Aβproduction and tau protein formation,regulate estrogen receptor and epidermal growth factor receptor,and regulate dopaminergic and cholinergic systems.