固本抗敏方治疗慢性荨麻疹的作用机制:基于网络药理学和分子对接  

Network pharmacology-based study on the mechanisms of Guben Kangmin Formula for the treatment of chronic urticaria

作　　者：谢宝琳 吴钉红[1,2,3] 卢传坚 XIE Baolin;WU Dinghong;LU Chuanjian(Second Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510120,China;Guangdong Provincial Academy of Chinese Medical Sciences,Guangzhou 510006,China;Second Affilated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120,China;State Key Laboratory of Traditional Chinese Medicine Syndrome,Guangzhou 510120,China)

机构地区：[1]广州中医药大学第二临床学院,广东广州510120 [2]广东省中医药科学院,广东广州510006 [3]广州中医药大学第二附属医院,广东广州510120 [4]中医证候全国重点实验室,广东广州510120

出　　处：《皮肤性病诊疗学杂志》2025年第3期196-205,共10页Journal of Diagnosis and Therapy on Dermato-venereology

基　　金：省部共建中医湿证重点实验室项目(SZ2021ZZ51);广州市科技计划项目(202206080006);国家中医药传承创新团队项目(ZYYCXTD-C-202204)。

摘　　要：目的基于网络药理学和分子对接的方法预测固本抗敏方治疗慢性荨麻疹的靶点及相关信号通路,探讨其治疗慢性荨麻疹的作用机制。方法通过中医药生物信息分析网站(TCMSP,BATMAN-TCM,贝尔斯坦数据库,CNPD)并查阅文献,筛查和预测固本抗敏方有效成分,与Drugbank收集的慢性荨麻疹小分子药物计算化学描述符进行比较,通过“rule of five”筛选类药性成分,并进一步与慢性荨麻疹小分子药物的功效进行主成分分析,得到潜在活性成分及其靶点;检索GeneCards和OMIM疾病数据库获取慢性荨麻疹疾病靶点,与潜在活性成分靶点通过映射取交集,作为固本抗敏方治疗慢性荨麻疹的作用靶标,并进行GO和KEGG通路富集分析;同时将作用靶标导入STRING数据库,对靶标间的相互作用进行分析,分析结果导入Cytoscape软件进行MCODE聚类和网络括扑性质分析,得到核心靶标,将核心靶标导入BioGPS数据库,分析核心靶标在皮肤和淋巴结以及CD4+T细胞和CD8+T细胞中的表达丰度,同时对核心靶标进行KEGG通路富集分析。结果检索得到固本抗敏方成分1124个和有关慢性荨麻疹西药小分子药物25种;类药性和主成分分析筛选出潜在活性成分349个,预测得到90个作用靶点;MCODE聚类和网络括扑性质分析得到HIF1A、IL6、MAPK3等10个等核心靶标,这些核心靶标在皮肤、淋巴结、CD4+T细胞、CD8+T细胞均有表达,且与炎症反应等多个生物过程、分子组成和细胞功能有关,其中包含HIF-1信号通路、TNF信号通路、Th17细胞分化、PI3K-Akt等多条信号通路。分子对接结果表明去氧紫草素、yinyanghuoA和9alpha-hydroxyfraxinellone-9-o-beta-d-glucosid等活性成分通过INS、MAPK3、JAK2等靶标调控GBKMF治疗银屑病的治疗机制。结论固本抗敏方治疗慢性荨麻疹具有多成分-多靶点-多通路特点,其作用机制可能与HIF-1信号通路、TNF信号通路、Th17细胞分化、PI3K-Akt等信号通Objective To predict the targets and signal pathways of Guben Kangmin Formula(GBKMF)in treating chronic urticaria(CU)based on network pharmacology and molecular docking methods,and to explore the mechanisms of its action.Methods The active ingredients in GBKMF were obtained from the databases of TCMSP,BATMAN-TCM,Berstein CNPD and literatures.The drug-like components were screened by“rule of five”after comparing with the computational chemical descriptors of small molecule drugs for CU.Principal component analysis(PCA)was further conducted,and potential active components and corresponding targets were obtained.Meanwhile,disease targets for CU were obtained from disease databases.The common targets of the potential active components of GBKMF and CU were explored and submitted to ClueGo and DAVID database for GO enrichment and KEGG pathway analyses.Afterwards,the common targets were submitted to STRING database to analyze the protein-protein interaction(PPI)for these targets.The results were imported into Cytoscape software for MCODE clustering and network topological property analyses to obtain the core targets.Then core targets were imported into BioGPS database to analyze the expression abundance of core targets in the skin,lymph nodes,CD4+T cells and CD8+T cells.At the same time,KEGG pathway enrichment analysis was performed for the core targets.Results A total of 1124 ingredients in GBKMF and 25 small molecule drugs for CU were retrieved.Through drug-likeness property and principal component analyses,349 potential active ingredients were screened,and 90 targets were predicted.The core targets such as HIF1A,IL6 and MAPK3 were obtained by MCODE clustering and topo logical property analyses.These core targets were expressed in the skin,lymph nodes,CD4+T cells,and CD8+T cells.GO analysis showed that these targets were associated with multiple biological processes,molecular composition,and cell function,such as inflammatory response,involving in the regulation of HIF-1 signaling pathway,TNF signaling pathway,Th1

关 键 词：慢性荨麻疹 固本抗敏方 网络药理学 分子对接 作用机制 

分 类 号：R758.25[医药卫生—皮肤病学与性病学]