基于网络药理学探讨四妙勇安汤治疗糖尿病足的作用机制  

Mechanism of Simiaoyong'an Decoction in the Treatment of Diabetic Foot Based on Network Pharmacology

作　　者：程亚清 牛少辉 曹乾 常金霞 方毅娜 王唱 白怡敏 曹建春[2] CHENG Yaqing;NIU Shaohui;CAO Qian;CHANG Jinxia;FANG Yina;WANG Chang;BAI Yimin;CAO Jianchun(Tsinghua University Yuquan Hospital,Beijing 100040,China;Dongfang Hospital of Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]清华大学玉泉医院,北京100040 [2]北京中医药大学东方医院,北京100078

出　　处：《西部中医药》2025年第1期73-79,共7页Western Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81874473)。

摘　　要：目的:基于网络药理学方法探讨四妙勇安汤治疗糖尿病足的作用机制。方法:利用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选金银花、玄参、当归、甘草的活性成分;利用Pub Chem、Swiss Target Prediction数据库筛选药物活性成分的相关靶点;通过人类基因数据库(the human gene database,Gene Cards)和在线人类孟德尔遗传(online mendelian inheritance in man,OMIM)数据库获取疾病相关靶点,将药物活性成分靶点与疾病靶点取交集后得到药物作用于疾病的潜在靶点,导入STRING数据库构建蛋白-蛋白互作(protein-protein interactions,PPI)网络,利用R 4.1.0软件提取网络核心基因,并对潜在作用靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;利用Cytoscape 3.7.2软件构建KEGG关系网络图。结果:筛选后共得到四妙勇安汤活性成分126个,相关靶点690个,药物作用于疾病的潜在靶点175个,核心靶点有ALB、Akt1、MAPK3、VEGFA、EGFR、TNF、CASP3等;核心靶点涉及负离子转运正调控、肽基丝氨酸修饰、肽基丝氨酸磷酸化等生物学过程,作用的位点主要有膜筏、膜微域、囊泡、分泌颗粒、顶端细胞等;分子功能有蛋白丝氨酸/苏氨酸激酶活性、蛋白络氨酸激酶活性等;涉及的通路包括MAPK、PI3K/Akt、AGE-RAGE、Ras、HIF-1等信号通路。结论:四妙勇安汤通过多成分、多靶点、多通路途径治疗糖尿病足,为四妙勇安汤的研究提供了理论依据。Objective:To explore the mechanism of Simiaoyong'an decoction in the treatment of diabetic foot based on network pharmacology.Methods:TCMSP was utilized to screen the active ingredients of Jinyinhua(Lonicerae japonicae flos),Xuanshen(Scrophulariae radix),Danggui(Angelicae sinensis radix)and Gancao(Glycyrrhizae radix et rhizoma);PubChem and SwissTargetPrediction database were applied in the screen of active ingredients of the drugs;disease-related targets were obtained from GeneCards and OMIM,and by intersecting the drug targets with the disease targets,the potential targets for drugs action on the disease were identified,introduced into STRING database to construct protein-protein interactions(PPI)network,R4.1.0 software was used to extract the network core genes,and perform GO and KEGG pathway enrichment analysis of the potential targets;KEGG network diagram was built using Cytoscape 3.7.2 software.Results:The study has yielded 126 active ingredients from the decoction,690 related targets and 175 potential targets for the drug acting on the disease,the core targets contain ALB,Akt1,MAPK3,VEGFA,EGFR,TNF and CASP3;the core targets are involved in positive regulation of negative ion transport,peptidylserine modification,peptidylserine phosphorylation and other biological processes,and the sites of action mainly cover membrane rafts,membrane microdomains,vesicles,secretory granules and apical cells,the molecular functions include protein serine/threonine kinase activity,protein tyrosine kinase activity,and the main pathways contain MAPK,PI3K/Akt,AGE-RAGE,Ras and HIF-1.Conclusion:The medicine could treat diabetic foot via multi-component,multi-target and multi-pathway,which could provide theoretical references for the study on the decoction.

关 键 词：糖尿病足 四妙勇安汤 网络药理学 作用机制 信号通路 

分 类 号：R255.4[医药卫生—中医内科学]