基于网络药理学探讨丹参-葛根药对治疗糖尿病心肌损伤的分子机制

Molecular Mechanism of Herbal Pair Danshen-Gegen in Treating Diabetic Myocardial Injury Based on Network Pharmacology

目的:采用网络药理学方法研究丹参-葛根药对治疗糖尿病心肌损伤的作用机制。方法:通过检索中药系统药理数据分析平台(TCMSP),以口服利用度(OB)≥30%,类药性(DL)≥0.18作为筛选条件,剔除预测不到靶点的化合物共得到41个有效成分,其中丹参38个,葛根3个,同时筛选出65个有效作用靶点。通过Genecard和OMIM数据库获得与糖尿病心肌损伤相关疾病的作用靶点580个,利用R语言软件包得到药对-疾病的交集靶点29个,并绘制韦恩图,利用Cytoscape 3.7.2软件构建药对-疾病-靶点作用关系网络图,用STRING在线软件绘制药物和疾病交集靶点蛋白相互作用网络,通过DAVID和Kabas3.0分析工具进行GO功能和KEGG通路富集分析。结果:GO分析结果显示,分子功能主要是蛋白质异二聚活性、类固醇激素受体活性、内肽酶活性、半胱氨酸型内肽酶活性、类固醇结合、配体调节序列特异性DNA结合-转录因子活性、半胱氨酸型肽酶活性、RNA聚合酶II转录因子结合、神经递质受体活性、核受体活性、细胞因子受体结合等。KEGG分析结果显示,丹参-葛根药对主要作用与凋亡信号通路、PI3K-Akt信号通路、TNF信号通路、IL-17信号通路、糖尿病并发症中的AGE-RAGE信号通路等。结论:应用网络药理学的研究方法通过多种数据库与统计分析软件可以有效预测与分析丹参-葛根药对主要是通过多途径、多种信号通路作用于多种靶点来发挥治疗糖尿病心肌损伤的机制。

To explore the action mechanism of the herb pair Danshen-Gegen in the treatment of diabetic myocardial injury by using network pharmacology.Methods:Effective components of Danshen-Gegen were screened out by traditional Chinese medicine systematic pharmacological(TCMSP)database,with oral bioavilability(OB)≥30%and drug-like(DL)≥18%selected as the thresholds.A total of 41 active ingredients were obtained by excluding compounds whose targets were not predicted,of which 38 were from Danshen and 3 were from Gegen,and 65 effective targets were screened simultaneously.GeneCards and OMIM database were used to obtain 580 active targets of diabetic myocardial injury.29 herbal pair-disease intersection targets were obtained by using R language package and Venne diagram was drawn.Interaction network diagram of herbal pair-disease-target was constructed by using the Cytoscape 3.7.2 software and the protein interactions network was constructed by using the String database and Cytoscape software.GO functions and KEGG pathway enrichment analysis were performed with DAVID and Kabas 3.0 analysis tools.Results:The GO analysis results showed that the molecular functions mainly involved protein heterodimer activity,steroid hormone receptor activity,endopeptidase activity,cysteine-type endopeptidase activity,steroid binding,ligand-regulating sequence-specific DNA binding-transcription factor activity,cysteine-type peptidase activity,RNA polymerase II transcription factor binding,neurotransmitter receptor activity,nuclear receptor activity,cytokine receptor binding and the like.The results of KEGG analysis showed that the main effects of Danshen-Gegen were related to apoptotic signal pathway,PI3 K-Akt signal pathway,TNF signal pathway,IL-17 signal pathway and AGE-RAGE signal pathway in diabetes complications.Conclusion:Applying research methods of network pharmacology through multiple databases and statistical analysis software can effectively predict and analyze the herbal pair Danshen-Gegen mainly through multiple pathways and multiple signaling pathways acting on multiple targets to treat diabetic myocardial injury.