基于网络药理学探讨地黄饮子“异病同治”阿尔茨海默病和糖尿病的作用机制  

Study on the mechanism of Dihuang Decoction in treating Alzheimer disease and diabetes mellitus with same method based on network pharmacology

作　　者：孙跃峰 侯志涛[1,2] 陈晶 Yuefeng Sun;Zhitao Hou;Jing Chen(Basic Medical College,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Key Laboratory of Chinese Internal Medicine of Ministry of Education,Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]黑龙江中医药大学基础医学院,哈尔滨150040 [2]北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京100700

出　　处：《国际中医中药杂志》2023年第6期743-748,共6页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82274395);黑龙江省普通本科高等学校青年创新人才培养计划项目(UNPYSCT-2020227)。

摘　　要：目的基于网络药理学方法探讨地黄饮子“异病同治”AD与糖尿病的共同药效物质基础及作用机制,提供生物信息学依据。方法检索TCMSP、中国知识资源总库(CNKI)中地黄饮子组方药物有效成分,结合UniProt数据库得到药物靶点,利用GeneCards、OMIM、TTD等数据库分别获得AD及糖尿病相关疾病靶点。采用Cytoscape 3.7.1软件构建“疾病-药物-成分-靶点”网络。使用R studio软件构建地黄饮子有效成分与疾病靶点的Circos关系图。利用STRING数据库构建PPI网络。通过DAVID数据库、Metascape、R studio软件进行GO功能和KEGG通路富集分析。结果获得地黄饮子活性成分206个,PPI网络筛选出51个关键靶点;GO分析主要富集于γ-氨基丁酸(GABA)、胆碱能突触、雌激素反应、BCL-2家族蛋白复合物等生物过程。KEGG分析主要富集于FoxO信号通路、HIF-1信号通路、胰岛素抵抗通路等。结论地黄饮子“异病同治”AD与糖尿病具有多成分、多靶点、多途径的协同作用特点,主要通过原花青素B7、原花青素B5、原花青素B1等活性成分,作用于TNF、IL-6、ESR1、PPARG、AKT1等靶点,调控FoxO信号通路、HIF-1信号通路等发挥作用。Objective To study the common pharmacodynamic substance basis and potential mechanism of Dihuang Decoction in treating Alzheimer disease(AD)and diabetes mellitus(DM)with same method based on network pharmacology;To provide bioinformatics basis.Methods The effective components of Dihuang Decoction were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and CNKI.The drug targets were obtained by combining and UniProt database.The targets of AD and DM related diseases were obtained by GeneCards,OMIM and TTD databases respectively.Cytoscape 3.7.1 software was used to construct the Disease-drug-component-target network.R studio software was used to construct a Circos diagram of the effective compounds and disease targets.Protein-protein interaction(PPI)network was constructed using STRING platform.GO enrichment and KEGG enrichment analysis was conducted through DAVID database,Metascape,R Studio software.Results A total of 206 active components were obtained;PPI network construction screened 51 key targets;GO enrichment analysis revealed the functions of GABA,cholinergic synapse,estrogen response,BCL-2 family protein complex and so on;KEGG enrichment analysis revealed FoxO signaling pathway,HIF-1 signaling pathway,insulin resistance pathway and other pathways.Conclusion Dihuang Decoction has the synergistic characteristics of multiple components,multiple targets and multiple pathways in treating AD and DM with same method,mainly through proanthocyanidin B7,proanthocyanidin B5,proanthocyanidin B1 and other active ingredients,acting on TNF,IL-6,ESR1,PPARG,AKT1 and other targets,regulating FoxO signaling pathway,HIF-1 signaling pathway,etc.

关 键 词：阿尔茨海默病 糖尿病 地黄饮子 异病同治 网络药理学 

分 类 号：R285[医药卫生—中药学]