首页|补阳还五汤"异病同治"2型糖尿病和阿尔兹海默症作用机制的网络药理学分析

补阳还五汤"异病同治"2型糖尿病和阿尔兹海默症作用机制的网络药理学分析

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目的 基于网络药理学和分子对接技术探讨补阳还五汤对 2 型糖尿病(T2DM)和阿尔兹海默症(AD)"异病同治"的作用机制.方法 借助TCMSP、SymMap等数据库检索和筛选补阳还五汤中 7 味组方中药的活性成分,并利用PharmMapper服务器对活性成分进行靶点预测.通过OMIM、DrugBank、GeneCards及Disgenet数据库收集T2DM和AD疾病相关靶点.对疾病相关靶点与活性成分作用靶点取交集,获得补阳还五汤"异病同治"T2DM和AD的潜在作用靶点.使用STRING数据库和Cytoscape软件分别构建潜在作用靶点的蛋白-蛋白互作(PPI)网络和"药物-成分-靶点"网络,通过网络拓扑分析筛选出核心活性成分和核心靶点.并借助Metascape数据库对潜在作用靶点进行GO功能及KEGG通路富集分析.采用AutoDock软件对筛选出的核心活性成分和核心靶点进行分子对接验证.结果 94 个补阳还五汤活性成分可作用于 342 个蛋白靶点,与 3 140 个AD疾病相关靶点和 1 708 个T2DM疾病相关靶点比对后,得到 100 个潜在作用靶点(交集靶点).GO功能富集分析显示,潜在作用靶点主要参与MAPK级联调控、激素介导的信号通路、细胞对脂质的反应、调节炎症反应等生物过程.KEGG通路富集分析得到MAPK、PI3K/Akt、FoxO、AGE/RAGE、胰岛素抵抗、脂质和动脉粥样硬化、非酒精性脂肪肝等通路.PPI 和"药物-成分-靶点"网络拓扑分析筛选出 MAPK8、MAPK14、GSK3B、PPARG等 10 个核心靶点,以及芍药苷、苯甲酰芍药苷、(+)-儿茶素等 10 个核心活性成分,分子对接结果表明上述成分与靶点均有较强的结合能力.结论 补阳还五汤可能通过芍药苷、儿茶素等核心成分,作用于PPARG、GSK3B等关键靶点,参与调控MAPK、PI3K/Akt等信号通路,进而发挥"异病同治"T2DM和AD的作用.
Network Pharmacology Analysis on Mechanism Study of Buyang Huanwu Decoction for"Treating Different Diseases with Same Therapies"in Type 2 Diabetes Mellitus and Alzheimer's Disease
Objective To explore the mechanism of Buyang Huanwu Decoction for"treating different diseases with same therapies"in type 2 diabetes mellitus(T2DM)and Alzheimer's disease(AD)based on network pharmacology and molecular docking techniques.Methods Firstly,the active ingredients of seven herbs in Buyang Huanwu Decoction were searched and screened by TCMSP,SymMap and other databases,the target prediction of these active ingredients was carried out by PharmMapper.The disease targets of T2DM and AD were collected from OMIM,DrugBank,GeneCards and Disgenet databases.The potential targets of Buyang Huanwu Decoction for"treating different diseases with same therapies"in T2DM and AD were obtained by intersecting with targets of active ingredients and the disease targets.Then STRING database and Cytoscape software were used to construct the PPI network and"herbs-components-targets"network,respectively.The core targets and pharmacodynamic components were screened through network topology analysis.Furthermore,GO functional and KEGG enrichment analysis was performed for potential targets using Metascape database.Finally,AutoDock software was used to verify the molecular docking between the selected components and targets.Results Ninety-four active components of Buyang Huanwu Decoction can act on 342 protein targets,and 100 intersection targets were obtained by comparing with 3 140 AD targets and 1 708 T2DM targets.GO functional enrichment analysis showed that these targets were mainly involved in MAPK cascade-mediated regulation,hormone-mediated signaling pathways,cellular response to lipids,regulation of inflammation response and other biological processes.MAPK,PI3K/Akt,FoxO,AGE/RAGE,insulin resistance,lipid and atherosclerosis,and non-alcoholic fatty liver signaling pathway were significantly enriched in KEGG analysis.PPI and topology analysis of"herbs-components-targets"network were used to screen out 10 core targets such as MAPK8,MAPK14,GSK3B,PPARG,and 10 core pharmacodynamic components such as paeoniflorin,benzoyl paeoniflorin,(+)-catechin.The results of molecular docking showed that these components had strong binding ability to the targets.Conclusion The core components of Buyang Huanwu Decoction,such as paeoniflorin and catechin,may act on PPARG,GSK3B and other key targets,and participate in the regulation of signaling pathways including MAPK and PI3K/Akt,which play a role in"treating different diseases with the same therapies"of T2DM and AD.

Buyang Huanwu Decoctiontype 2 diabetes mellitusAlzheimer's diseasetreating different diseases with the same therapiesnetwork pharmacologymolecular docking

薛慧、徐艳明、姜晶、孟雪彤、刘书萌、周倩、雷霞、张宁

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黑龙江中医药大学药学院,黑龙江哈尔滨 150040

黑龙江中医药大学佳木斯学院,黑龙江 佳木斯 154007

南京中医药大学无锡附属医院/江苏省中医退行性骨关节病临床医学创新中心,江苏 无锡 214071

补阳还五汤 2 型糖尿病 阿尔兹海默症 异病同治 网络药理学 分子对接

黑龙江省中医药管理局科研项目中央支持地方高校改革发展资金人才培养项目黑龙江中医药大学科研基金项目黑龙江中医药大学科研基金项目黑龙江中医药大学科研基金项目

ZHY2023-051黑财教2021137号文件2018192019BJP012018pt04

2024

中药新药与临床药理
广州中医药大学

中药新药与临床药理

CSTPCD北大核心
影响因子:0.908
ISSN:1003-9783
年,卷(期):2024.35(9)