摘要
目的采用网络药理学方法和分子对接技术,探索芍药甘草汤治疗特应性皮炎的作用机制。方法通过中药系统药理学数据库和分析平台获取芍药甘草汤的活性成分及其对应靶点;在Disgenet、Genecards、PharmGkb、TTD和OMIM数据库中获取特应性皮炎相关靶点;将药物-疾病共有靶标导入STRING数据库进行蛋白质-蛋白质相互作用分析;利用Cytoscape 3.9.1软件构建疾病-成分-靶点网络,并利用R软件进行GO功能分析与KEGG通路富集分析;利用AutoDock Vina软件对其进行分子对接,确定芍药甘草汤主要活性成分与核心靶点相互作用的分子基础。结果获得芍药甘草汤有效活性成分93种,潜在作用靶点244个,与特应性皮炎疾病共同作用靶点85个。药物-成分-关键靶点-网络分析结果显示山柰酚、β-谷甾醇、芍药苷、槲皮素、芒柄花素、甘草查尔酮a和柚皮素等是芍药甘草汤治疗特应性皮炎的关键成分,并筛选出21个关键靶点。GO富集分析结果显示,芍药甘草汤主要涉及膜筏、膜微区、转录调节复合物等分子组成,影响转录共调节结合、DNA结合转录因子结合、核受体活性等分子功能,参与对细胞外刺激的反应、对活性氧的反应以及对氧化应激的反应等生物过程;KEGG通路富集分析涉及163条通路,涉及TNF信号通路、Th17细胞分化、Toll样受体信号通路、HIF-1信号通路、IL-17信号通路以及肿瘤相关信号通路等;分子对接结果验证了芍药甘草汤主要活性成分可与对应核心靶点蛋白形成稳定的对接模型。结论应用网络药理学方法预测了芍药甘草汤治疗特应性皮炎的主要有效成分及潜在靶点,初步揭示了芍药甘草汤治疗特应性皮炎的物质基础和作用机制,为后续研究提供了思路与依据。
Objective To explore the mechanism of Shaoyao Gancao decoction in the treatment of atopic dermatitis using network pharmacology and molecular docking.Methods The active components and their corresponding targets of Shaoyao Gancao decoction were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform.The Disgenet,Genecards,PharmGkb,TTD and OMIM databases were searched to predict the targets related to atopic dermatitis.The shared targets were imported into the STRING database for protein-protein interaction analysis.The disease-componenttarget network was constructed using Cytoscape 3.9.1 software,and GO function analysis and KEGG pathway enrichment analysis were performed using R packages.Molecular docking was carried out with AutoDock Vina to determine the molecular basis of interactions between the main active components of Shaoyao Gancao decoction and the core targets.Results A total of 93 active ingredients and 244 corresponding targets were obtained for Shaoyao Gancao decoction,so were 85 common targets of Shaoyao Gancao decoction and atopic dermatitis.The drug-component-target network analysis showed that kaempferol,β-sitosterol,paeoniflorin,quercetin,formononetin,licorice chalcone a and naringenin were the specific therapeutic properties of Shaoyao Gancao decoction,and 21 corresponding key targets were screened out.The GO enrichment analysis showed that Shaoyao Gancao decoction mainly involved molecular composition of membrane rafts,membrane microdomains,and transcriptional regulatory complexes,affected molecular functions of transcriptional co-regulator binding,DNA-binding transcription factor binding,and nuclear receptor activity,and participated in such biological processes as response to extracellular stimuli,reactive oxygen species,and to oxidative stress.KEGG pathway enrichment analysis involved 163 pathways,including the TNF signaling pathway,Th17 cell differentiation,Toll-like receptor signaling pathway,HIF-1 signaling pathway,IL-17 signaling pathway,and tumor-related signaling pathway.Molecular docking results verified that the main active components of Shaoyao Gancao decoction could form a stable docking model with the corresponding core target protein.Conclusion The main effective components and potential targets of Shaoyao Gancao decoction in the treatment of atopic dermatitis are predicted by network pharmacology,and the material basis and mechanism are revealed,which provides new ideas and reference for further in-depth study.
作者
刘燕
汤小涵
袁海龙
高茸
LIU Yan;TANG Xiao-han;YUAN Hai-long;GAO Rong(Air Force Medical Center,PLA,Beijing 100142,China)
出处
《解放军药学学报》
CAS
2022年第6期471-478,共8页
Pharmaceutical Journal of Chinese People's Liberation Army
基金
空军特色医学中心临床研究项目,No.2021LC005。
关键词
芍药甘草汤
特应性皮炎
网络药理学
分子对接
Shaoyao Gancao decoction
atopic dermatitis
network pharmacology
molecular docking
