基于网络药理学探讨丹参-红花药对治疗糖尿病周围神经病变的作用机制  

Network Pharmacology-based Exploration into the Mechanism of Danshen-Honghua Couplet Medicines in the Treatment of Diabetic Peripheral Neuropathy

作　　者：陈方飞 刘雅玲 罗幸 麦小丽 邓小敏 CHEN Fangfei;LIU Yaling;LUO Xing;MAI Xiaoli;DENG Xiaomin(Guangxi University of Chinese Medicine,Nanning 530001,China;The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China)

机构地区：[1]广西中医药大学,广西南宁530001 [2]广西中医药大学第一附属医院,广西南宁530023

出　　处：《西部中医药》2025年第4期47-52,共6页Western Journal of Traditional Chinese Medicine

基　　金：广西医疗卫生适宜技术开发与推广应用项目(S2018105);广西中医药大学自然科学基金面上项目(2020MS019)。

摘　　要：目的:运用网络药理学方法探讨丹参-红花药对治疗糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)的作用机制。方法:通过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)检索丹参和红花的活性成分及对应靶点,借助UniProt数据库对靶点进行规范化;通过人类基因数据库(the human gene database,GeneCards)、Disgenet、药物靶标数据库(therapeutic targetdatabase,TTD)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)获取DPN的相关靶点,并利用R语言筛选药物与疾病的交集靶点;通过STRING数据库对交集靶点进行蛋白-蛋白互作(protein-protein interactions,PPI)网络分析,并通过Bioconductor平台对交集靶点进行基因本体论(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;通过Cytoscape软件构建丹参-红花药对治疗DPN的“活性成分-疾病靶点”可视化调控网络及PPI调控网络,借助CytoNCA插件筛选并提取出核心调控网络得到的核心活性成分及作用靶点。结果:获得丹参-红花药对73个活性成分,对应215个作用靶点,其中与疾病的交集靶点96个;筛选出槲皮素、山柰酚、木犀草素、丹参酮ⅡA等16个核心活性成分,核心作用靶点包括AKT1、IL-1β等20个;GO功能富集分析涉及2497个条目,主要影响转录因子活性、酶活性、受体活性及生物化学过程调控等过程,KEGG通路富集分析得到158条,涉及到糖尿病并发症中的AGE-RAGE、IL-17、TNF等信号通路。结论:丹参-红花药对通过槲皮素、山柰酚、木犀草素、丹参酮ⅡA等活性成分干预AGE-RAGE等信号通路,并作用于AKT1等靶点,从而发挥治疗DPN的作用。Objective:To discuss the mechanism of Danshen(Salviae miltiorrhizae radix et rhizoma)-Honghua(Carthami flos)couplet medicines in the treatment of diabetic peripheral neuropathy(DPN)using network pharmacology.Methods:The active ingredients and the corresponding targets of the two drugs were searched from TCMSP,and the standardization of the targets were performed via UniProt database;DPN-related targets were gained from GeneCards,Disgenet,TTD and OMIM,the intersecting targets of medicine and disease were screened utilizing R language;protein-protein interactions(PPI)network analysis of the intersection targets was conducted via STRING database,GO enrichment analysis and KEGG enrichment analysis of the intersection targets were performed via Bioconductor platform;Cytoscape software was utilized to construct visual control network and PPI regulation network of"active ingredients-disease targets"of the couplet medicines in the treatment of DPN,the core active ingredients and the targets of action of the core regulatory network were screened and extracted by CytoNCA plug-in.Results:The study has gained 73 active ingredients related to the couplet medicines,corresponding to 215 targets of action,among them,there were 96 targets intersected with disease;16 core active ingredients including quercetin,kaempferol,luteolin,tanshinone II A and others were screened,and there were 20 core targets of action containing AKT1,IL-1βand others;GO functional enrichment analysis involved 2497 items,mainly affecting the regulation of transcription factor activity,enzyme activity,receptor activity and biochemical processes,KEGG pathway enrichment analysis has obtained 158 pathways,involving signaling pathways such as AGE-RAGE,IL-17 and TNF in diabetic complications.Conclusion:Danshen-Honghua couplet medicines acts on the targets including AKT1 and others by intervention on AGE-RAGE signaling pathways via the active ingredients containing quercetin,kaempferol,luteolin,tanshinone II A and others,thereby treating DPN.

关 键 词：糖尿病周围神经病变 丹参 红花 网络药理学 

分 类 号：R285[医药卫生—中药学]