基于网络药理学与分子对接探讨运脾化湿清肺汤治疗特应性皮炎的作用机制  

Study on the Mechanism of Action of Spleen-Activating and Dampness-Resolving and Lung-Clearing Decoction in the Treatment of Atopic Dermatitis Based on Network Pharmacology and Molecular Docking

作　　者：常秋伊 倪骥杰 宋瑜[3] CHANG Qiuyi;NI Jijie;SONG Yu(Guangming Hospital of Traditional Chinese Medicine of Pudong New Area of Shanghai,Shanghai,China,201399;Shanghai Minhang District Pujiang Community Health Service Center,Shanghai,China,201112;Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China,200032)

机构地区：[1]上海浦东新区光明中医医院,上海201399 [2]上海市闵行区浦江社区卫生服务中心,上海201112 [3]上海中医药大学附属龙华医院,上海200032

出　　处：《河南中医》2024年第3期367-373,共7页Henan Traditional Chinese Medicine

基　　金：上海市科学技术委员会“科技创新行动计划”医学创新研究专项项目(20Y21901500)。

摘　　要：目的:基于网络药理学与分子对接探讨运脾化湿清肺汤治疗特应性皮炎(atopic dermatitis,AD)的作用机制。方法:运用中药网络药理学分析系统(TCM network pharmacology analysis system,TCMNPAS)v1.0获取运脾化湿清肺汤(陈皮、枳壳、桑叶、菊花、金银花、黄芩、土茯苓、白鲜皮、白术、甘草)的活性成分和作用靶点。运用GeneCards数据库、DrugBank数据库检索相关文献获取AD疾病靶点,并借助jvenn平台得到运脾化湿清肺汤与AD的交集靶点。将交集靶点上传至STRING数据库,构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络。通过Cytoscape 3.8.0软件进行拓扑分析,从而筛选核心靶点。采用Metascape数据库进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。利用Cytoscape 3.8.0软件构建“药物-活性成分-作用靶点”网络、“药物-靶点-通路”网络。最后,通过TCMNPAS数据库进行分子对接验证。结果:运脾化湿清肺汤活性成分243个、作用靶点344个。AD疾病靶点145个,两者的交集靶点15个。针对PPI网络进行拓扑分析,筛选得到4个核心靶点,即白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子(tumor necrosis factor,TNF)、CXC基序趋化因子配体8(C-X-C motif chemokine ligand 8,CXCL8)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)。GO功能分析主要涉及对病毒、细菌、脂多糖的应答及细胞因子受体结合、转录因子结合等。KEGG通路55条,主要涉及TNF信号通路、叉头框蛋白O(forkhead box protein O,FoxO)信号通路、低氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路等。分子对接表明核心成分与活性靶点具有较好的亲和性和结合能力。结论:运脾化湿清肺汤可能通过三甲氧基黄酮、陈皮素、孕烷醇酮等活性成分作用于IL-6、TNF、CXCL8、MAPK1等靶点,调控TNF、FoxO、HIF-1等信号通�Objective:To study on the mechanism of action of Spleen-Activating and Dampness-Resolving and Lung-Clearing Decoction on atopic dermatitis(AD) based on network pharmacology and molecular docking.Methods:The targets and active components of Spleen-Activating and Dampness-Resolving and Lung-Clearing Decoction,such as Chenpi(Pericarpium Citri Reticulatae),Zhiqiao(Fructus Aurantii),Sangye(Folium Mori),Juhua(Flos Chrysanthemi),Jinyinhua(Flos Lonicerae Japonicae),Huangqin(Radix Scutellariae),Tufuling(Rhizoma Smilacis Glabrae),Baixianpi(Cortex Dictamni),Baizhu(Rhizoma Atractylodis Macrocephalae) and Gancao(Radix Glycyrrhizae),were obtained by TCM Network Pharmacology Analysis System(TCMNPAS) v1.0 and literature retrieval.AD disease targets were obtained by GeneCards database,DrugBank database and literature retrieval,and the intersection targets of Spleen-Activating and Dampness-Resolving and Lung-Clearing Decoction and AD were obtained by jvenn platform.The intersection targets were uploaded to STRING database to construct protein-protein interaction(PPI) network.Topological analysis was performed by Cytoscape 3.8.0 software to screen core targets.Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed by Metascape database.The "drug-active component-target" network and "drug-target-pathway" network were constructed by Cytoscape 3.8.0 software.Finally,molecular docking was verified by TCMNPAS database.Results:There were 243 active ingredients and 344 targets in Spleen-Activating and Dampness-Resolving and Lung-Clearing Decoction.There were 145 AD disease targets and 15 intersection targets between AD and PPI.Four core targets were screened out by topological analysis of PPI network,namely interleukin-6(IL-6),tumor necrosis factor(TNF),C-X-C motif chemokine ligand 8(CXCL8) and mitogen-activated protein kinase 1(MAPK1).GO function analysis mainly involved response to virus,bacteria,lipopolysaccharide,cytokine receptor binding and transcription factor binding.There were 55 KE

关 键 词：运脾化湿清肺汤 特应性皮炎 网络药理学 分子对接 作用机制 

分 类 号：R275.9[医药卫生—中西医结合]