基于网络药理学及分子对接探究菖菊止动方核心药物治疗抽动障碍的作用机制  

Mechanism of the Core Drugs of Changju Zhidong Prescription in the Treatment of Tic Disorders Based on Network Pharmacology and Molecular Docking Technology

作　　者：李园 程爽 孙婷[1] 张蔷 刘远欧 翟睿 王俊宏[1] Li Yuan;Cheng Shuang;Sun Ting;Zhang Qiang;Liu Yuan’ou;Zhai Rui;Wang Junhong(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700

出　　处：《儿科药学杂志》2023年第2期1-7,共7页Journal of Pediatric Pharmacy

基　　金：北京中医药大学王俊宏教学名师工作坊项目,编号MSGZF-201818;北京中医药大学新教师启动基金项目,编号2020-JYB-XJSJJ-040。

摘　　要：目的:基于网络药理学及分子对接探讨菖菊止动方核心药物治疗抽动障碍(TD)的作用机制。方法:基于文献研究及检索中药系统药理数据库与分析平台(TCMSP),挖掘菖菊止动方中核心药物的活性成分并预测其活性成分作用靶点,检索Drugbank、Genecards、OMIM、DisGeNET和TTD数据库,筛选TD相关靶基因,并与药物靶点取交集。应用Cytoscape 3.7.2软件构建“中药-活性成分-靶点”网络并进行拓扑分析,利用STRING数据库构建蛋白互作网络并筛选出核心靶点,利用DAVID数据库对交集靶点进行生物过程分析和通路富集分析。通过AutoDock Vina和Pymol将获得的核心成分和核心靶点进行分子对接。结果:筛选出菖菊止动方核心药物中活性成分81个,相关潜在靶点283个;筛选出TD相关靶基因2250个,提取交集靶点125个,筛选出核心靶点18个,主要为蛋白激酶B1(AKT1)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF)、白细胞介素1β(IL-1β)、雌激素受体1(ESR1)等;共有靶点主要富集在神经活性配体-受体相互作用、钙信号通路、T细胞受体信号通路等通路上,与对雌二醇的反应、化学性突触传递、免疫反应过程等相关。分子对接结果显示核心成分与靶点具有较好的结合活性。结论:菖菊止动方核心药物通过多成分、多靶点、多通路对TD发挥治疗作用。Objective:To explore the mechanism of the core drugs of Changju Zhidong prescription in the treatment of tic disorders(TD)by network pharmacology.Methods:Based on literature research and retrieval of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),we obtained the active ingredients of the core drugs in Changju Zhidong prescription,and predicted their targets.Drugbank,Genecards,OMIM,DisGeNET and TTD databases were used to search TD-related target genes,and they were intersected with the drug targets.Cytoscape 3.7.2 was used to construct the“drug-active ingredients-targets”network and conduct topological analysis.STRING database was used to construct the protein-protein interaction network and screen out the key targets.GO biological process analysis and KEGG pathway enrichment analysis were performed based on DAVID.AutoDock Vina and Pymol were used to dock the molecules of the key ingredients with the key targets.Results:A total of 81 active ingredients and 283 related potential targets were screened out.A total of 2,250 TD-related target genes were screened out,125 key targets were extracted,and 18 core targets were screened out,including protein kinase B1(AKT1),interleukin-6(IL-6),tumor necrosis factor(TNF),interleukin-1β(IL-1β)and estrogen receptor 1(ESR1).Common targets were mainly concentrated in neuroactive ligand-receptor interaction,calcium signaling pathway,T cell receptor signaling pathway and other pathways,which were related with response to estradiol,chemical synaptic transmission,and immune response.The results of molecular docking showed that the key ingredients have a good binding activity with the key targets.Conclusion:The core drugs of Changju Zhidong prescription play a therapeutic role on TD through multiple ingredients,multiple targets,and multiple pathways regulation.

关 键 词：抽动障碍 菖菊止动方 网络药理学 分子对接 

分 类 号：R961.1[医药卫生—药理学]