基于数据挖掘和网络药理学探讨中药干预阿尔茨海默病机制

Study on mechanism of traditional Chinese medicine intervention in Alzheimer's disease based on data mining and network pharmacology

中文关键词: 阿尔茨海默病  中药  网络药理学  分子对接  数据挖掘

英文关键词: Alzheimer's disease  traditional Chinese medicine  network pharmacology  molecular docking  data mining

中文摘要:

      目的 基于数据挖掘和网络药理学探讨中药治疗阿尔茨海默病的作用机制.方法 于Disgenet数据库、Gene-cards数据库中收集整理阿尔茨海默病备选靶点,借助String数据库构建蛋白相互作用(PPI)网络,进一步筛选疾病靶点,在TCMSP平台检索靶点对应药物成分与中药,并对中药性味归经进行统计分析,利用CytoScape3.9.1 构建"靶点—成分"与"靶点—成分—中药"网络,筛选出核心靶点与核心成分,最后在AutoDockTools-1.5.7 中进行分子对接验证.结果 获得阿尔茨海默病备选靶点275 个,靶点11 个,药物成分40 种,中药300 味,核心成分包含槲皮素、山柰酚、木犀草素、β-胡萝卜素、柚皮素、金合欢素、薯蓣皂苷元、汉黄芩素、黄芩素和花生四烯酸,核心靶点为TNF、TP53、IL6、AKT1、EGFR,核心成分与核心靶点能自发进行分子对接.中药性味多为寒、温、苦,主要归于肝经.结论 黄酮类化合物、β-胡萝卜素、薯蓣皂苷元和花生四烯酸可能是干预AD的潜在成分.

英文摘要:

      Objective To study the mechanism of traditional Chinese medicine in the treatment of Alzheimer's disease(AD)based on data mining and network pharmacology.Methods The candidate AD targets were collected from Disgenet da-tabase and Genecards database.The String database was used to construct a protein-protein interaction(PPI)network for fur-ther screening AD targets.TCMSP platform was used to screen the target-associated ingredients and herbs,and statistical analy-ses were performed to characterize the properties of these herbs including flavor,property and meridian entry.CytoScape 3.9.1 was used to construct"target-compound"and"target-compound-herbs"networks,and then the core targets and ingredients were screened.Furthermore,AutoDock Tools-1.5.7 was used to conduct molecular docking validation.Results 275 candi-date targets and 11 primary targets for AD were identified.40 ingredients and 300 herbs were obtained.The core ingredients in-cluded quercetin,kaempferol,luteolin,beta-carotene,naringenin,acacetin,diosgenin,wogonin,baicalein and arachidonic acid.The core targets were TNF,TP53,IL6,AKT1 and EGFR.The core ingredients could spontaneously dock with the core targets.The nature and flavor of the herbs were mostly cold,warm and bitter,and mainly attributed to the liver meridian.Conclusion Flavonoids,beta-carotene,diosgenin and arachidonic acid may be potential ingredients for the intervention of AD.