摘要
目的:基于网络药理学及分子对接技术探讨天麻钩藤饮治疗抽动障碍(TD)的作用机制。方法:通过中药系统药理数据库和分析平台(TCMSP)、BATMAN-TCM数据库筛选天麻钩藤饮的有效成分和作用靶点,利用GeneCards、 CTD、 DisGeNET、 OMIM、 PharmGKB和TTD数据库筛选TD的相关靶点,并通过VENNY2.1.0软件获取天麻钩藤饮治疗TD的交集靶点;使用STRING数据库构建靶点蛋白质互作网络,使用Cytoscape3.7.2软件构建中药-活性成分-靶点网络;运用R软件将关键靶点进行基因本体论(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析;采用分子对接技术对主要活性成分和关键靶点的结合能力进行验证。结果:共获得天麻钩藤饮活性成分205个,对应靶点756个,TD相关靶点4 072个。天麻钩藤饮治疗TD关键靶点有V-JUN肉瘤病毒癌基因同源物(JUN)、蛋白激酶B (AKT1)、信号传导转录激活因子(STAT3)、肿瘤蛋白p53 (TP53)、V-rel网状内皮细胞病毒癌基因同源物(RELA)、半胱氨酸天冬氨酸蛋白水解酶3 (CASP3)等。GO富集分析得到3 035条生物过程(BP)、166个细胞组成(CC)及307种分子功能(MF)。KEGG通路富集分析显示,天麻钩藤饮治疗TD涉及环磷酸腺苷(cAMP)、钙离子信号通路(Calcium)、丝裂原活化蛋白激酶(MAPK)、白细胞介素-17 (IL-17)和肿瘤坏死因子(TNF)等信号通路。分子对接发现主要活性成分(槲皮素、亚麻酸、α-亚麻酸、蔗糖、育亨宾)与关键靶点(JUN、AKT1、STAT3、TP53、RELA、CASP3)具有较好对接活性。结论:天麻钩藤饮治疗TD的作用机制与复方中槲皮素、亚麻酸、α-亚麻酸等成分作用于JUN、AKT1、STAT3、TP53、RELA等靶点调控cAMP、Calcium、MAPK、IL-17和TNF等信号通路有关。
Objective:To explore the mechanism of Tianma Gouteng Decoction in treating tic disorders(TD)based on network pharmacology and molecular docking technology.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and BATMAN-TCM database were searched for the active ingredients and targets of Tianma Gouteng Decoction;the related targets of tic disorders were screened from GeneCards,CTD,DisGeNET,OMIM,PharmGKB and TTD databases;the intersection targets of the treatment of TD with Tianma Gouteng Decoction were obtained by VENNY2.1.0 software.The target-protein interaction network was established by STRING database and the Chinese medicine-active ingredients-target network by Cytoscape3.7.2.The analysis of Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway on key targets was respectively performed using R language software and the ability of major active ingredients to bind to key targets was verified by molecular docking technology.Results:A total of 205 active ingredients and 756 corresponding targets from Tianma Gouteng Decoction,and 4072 related targets of TD were obtained.The key targets of Tianma Gouteng Decoction treating TD were recombinant V-JUN sarcoma virus 17 oncogene homolog(JUN),protein kinase B(AKT1),signal transducer and activator of transcription 3(STAT3),tumor protein p53(TP53),V-rel reticuloendotheliosis viral oncogene homolog A(RELA),cysteinyl aspartate specific proteinase 3(CASP3),etc.The GO enrichment analysis suggested 3035 biological processes(BP),166 cell component(CC)and 307 molecular functions(MF).KEGG pathway enrichment analysis showed that the treatment of TD by Tianma Gouteng Decoction involved cyclic adenosine monophos-phate(cAMP),Calcium,mitogen-activated protein kinases(MAPK),interleukin-17(IL-17),tumor necrosis factor(TNF)signaling pathways.According to molecular docking technology,the main active ingredients(quercetin,linolenic acid,α-linolenic acid,sucrose and m-hydroxybenzoic acid)had good binding activity with key targets(JUN,AKT1,STAT3,TP53,RELA and CASP3).Conclusion:The mechanism of Tianma Gouteng Decoction in treating TD is related to the effects of quercetin,linolenic acid,α-linolenic acid and other components on such targets as JUN,AKT1,STAT3,TP53 and RELA to regulate cAMP,Calcium,MAPK,IL-17 and TNF signaling pathways.
作者
华智超
刘力维
陈玉燕
程申
HUA Zhichao;LIU Liwei;CHEN Yuyan;CHENG Shen(The First Clinical Medical School of Zhejiang Chinese Medical University,Hangzhou Zhejiang 310053,China;Department of Pediatrics,The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou Zhejiang 310006,China)
出处
《新中医》
CAS
2024年第18期199-208,共10页
New Chinese Medicine
基金
浙江省中医药管理局共建科技计划项目(GZY-ZJ-KJ-23014)
浙江省中医药科技计划项目(2024ZL430,2024ZR084,2024ZF069)。
关键词
抽动障碍
天麻钩藤饮
网络药理学
分子对接
作用机制
Tic disorders
Tianma Gouteng Decoction
Network pharmacology
Molecular docking
Mechanism
