整合网络药理学和分子对接的二氢杨梅素抗抑郁作用机制研究  

Mechanism of Antidepressant Action of Dihydromyricetin by Integrating Network Pharmacology and Molecular Docking

作　　者：黄艳 陈好 蒋琳 李湘 仝宇航 颜伟健[2] 王乐[1] HUANG Yan;CHEN Hao;JIANG Lin(Puai Medical College,Shaoyang University,Shaoyang City,Hu’nan Province 422000)

机构地区：[1]邵阳学院普爱医学院,湖南省邵阳市422000 [2]邵阳学院附属第二医院

出　　处：《医学理论与实践》2024年第17期2885-2888,2909,共5页The Journal of Medical Theory and Practice

基　　金：湖南省自然科学基金项目(2022JJ50209);国家级大学生创新创业训练计划项目(202210547024)。

摘　　要：目的:应用网络药理学和分子对接方法探究二氢杨梅素(DHM)抗抑郁的作用机制。方法:通过TCMSP、Pubchem、PharmMapper、BATMAN-TCM、Swiss Target Predictio、SEA、STITCH数据库检索二氢杨梅素的潜在作用靶点,OMIM、GeneCards、DisGeNet数据库检索抑郁症潜在相关靶点,利用venny 2.1.0网站获取DHM与抑郁症的交集基因。基于matescape在线工具进行交集靶点GO功能注释和KEGG富集分析,利用STRING在线分析工具和Cytoscape3.9.1软件构建蛋白—蛋白互作(PPI)网络图,对其进行拓扑学分析,获得核心靶点。利用autodock vina 1.5.6软件进行分子对接。结果:网络药理学筛选得出110个DHM与抑郁症共同靶点。GO富集默认值筛选得出前20条潜在作用通路,KEGG pathway富集分析筛选出11条DHM抗抑郁的潜在作用通路。PPI网络分析核心靶点可能为:热休克蛋白90α家族A类成员1(HSP90AA1)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、表皮生长因子受体(EGFR)、血管内皮生长因子A(VEGFA)、丝裂原活化蛋白激酶1(MAPK1)、鼠肉瘤病毒癌基因(HRAS)、半胱氨酸—天冬氨酸蛋白酶3(CASP3)、雌激素受体1(ESR1)、血清白蛋白(ALB)、低氧诱导因子(HIF1A)等。分子对接显示DHM能与核心靶点较好地结合。结论:DHM抗抑郁具有多靶点、多通路协同的特点,可经MAPK、PI3K-AKT、Ras、癌症、癌症中的MicroRNAs途径、脂质与动脉粥样硬化、AGE-RAGE等信号通路,通过HSP90AA1、AKT1、EGFR、VEGFA、MAPK1、HRAS、CASP3、ESR1、ALB、HIF1A等协调抗抑郁作用,改善抑郁样行为。Objective:The mechanism of dihydromyricetin(DHM)against depression was investigated by network pharmacology and molecular docking.Methods:The potential targets of dihydromyricetin were searched through TCMSP,Pubchem,PharmMapper,BATMAN-TCM,Swiss Target Predictio,SEA and STITCH database.The OMIM,GeneCards and DisGeNet databases were used to search potential related targets of depression,and venny 2.1.0 was used to obtain the intersecting genes of DHM and depression.GO functional annotation and KEGG enrichment analysis of the intersecting targets were performed based on the matescape online tool.The protein-protein interaction(PPI)network diagram was constructed using the STRING online analysis tool and Cytoscape 3.9.1 software,and topological analysis was performed to obtain core targets.Molecular docking was performed using autodock vina 1.5.6 software.Results:Network pharmacology screening yielded 110 common targets of DHM and depression.The top 20 potential pathways were identified by GO enrichment default value,and 11 potential pathways were identified by KEGG pathway enrichment analysis.The core targets of PPI network analysis may be:heat shock protein 90αfamily class A member 1(HSP90AA1),serine/threonine protein kinase 1(AKT1),epidermal growth factor receptor(EGFR),vascular endothelial growth factor A(VEGFA),mitogen-activated protein kinase 1(MAPK1),murine sarcoma viral oncogene(HRAS),cysteine-aspartate protease 3(CASP3),estrogen receptor 1(ESR1),serum albumin(ALB),hypoxia-inducible factor(HIF1A),etc.Molecular docking showed that DHM could bind well to the core target.Conclusion:DHM antidepressant has the characteristics of multi-target and multi-pathway synergism,which can coordinate antidepressant effects and improve depressive-like behaviors via signaling pathways such as MAPK,PI3K-AKT,Ras,Cancer,MicroRNAs pathway in cancer,Lipids and Atherosclerosis,and AGE-RAGE,via HSP90AA1,AKT1,EGFR,VEGFA,MAPK1,HRAS,CASP3,ESR1,ALB,and HIF1A.

关 键 词：二氢杨梅素 抑郁症 网络药理学 分子对接 

分 类 号：R96[医药卫生—药理学]