基于网络药理学探讨加味二至丸治疗动脉粥样硬化的作用机制

Mechanism of Modified Erzhiwan Combined with Epimedium for Atherosclerosis Based on Network Pharmacology

目的:运用网络药理学研究方法探讨加味二至丸治疗更年期女性动脉粥样硬化的作用机制。方法:在中药系统药理学分析平台(TCMSP)和中药分子机制的生物信息学分析工(BATMAN-TCM)筛选加味二至丸的成分和靶点;并通过相关数据库检索动脉粥样硬化相关靶点;通过韦恩图得到加味二至丸和动脉粥样硬化的共同靶点,利用Cytoscape 3.6.1建立成分-疾病-靶点作用网络,然后使用STRING网站进行化合物-疾病共同靶点蛋白互作分析、运用Cytoscape 3.6.1进行可视化,并使用复合分子检测法(MCODE)分析重要模块;利用David数据库进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:筛选出加味二至丸38个成分和266个预测靶点,动脉粥样硬化靶点254个;通过韦恩图得到共同靶点52个,筛选出14个关键基因;这些共同靶点涉及炎症反应、调节胰岛素分泌、一氧化氮的合成调节等生物学过程;生物学通路包括肿瘤坏死因子信号通路、核转录因子-κB(NF-κB)信号通路、过氧化物酶体增殖物激活受体信号通路等22条信号通路。结论:加味二至丸可能通过雌激素受体调节雌激素水平,并可能通过抑制炎症反应,改善胰岛素抵抗等机制治疗动脉粥样硬化。

Objective:In this study,a network pharmacology-based method was applied to analyze the mechanism of modified Erzhiwan combined with epimedium in treatment of atherosclerosis.Method:The compounds and targets of modified Erzhiwan combined with epimedium were screened in traditional Chinese medicine(TCM)systems pharmacology database and analysis platform(TCMSP)and bioinformatics analysis tool for molecular mechanism of TCM(BATMAN-TCM).Mang related databases were applied to find the target-related to atherosclerosis.The common targets of modified Erzhiwan combined with epimedium and atherosclerosis were got by venn diagrams.Cytoscape 3.6.1 was used to construct ingredients-disease-targets networks.Then proteinprotein interaction(PPI)analysis of ingredients-disease-targets was builed in STRING database,and was visualized by Cytoscape 3.6.1,then important modules were analyzed with Moleculaar complex detection(MCODE).Biological information annotation databases(DAVID)was used to carry on gene ontology(GO)analysis and enrichment analysis of gene encyclopedia kyoto encyclopedia of genes and genomes(KEGG)pathway.Result:A total of 38 active ingredients and 266 potential targets of modified Erzhiwan combined with epimedium were obtained from TCMSP and BATMAN-TCM,254 atherosclerosis-related targets were retrieved from disease database.Then 52 common targets were obtained and 14 core genes were screened.Biological processes were related to inflammatory response,regulation of insulin secretion,positive regulation of nitric oxide biosynthetic process,etc.The biological pathways mainly included tumor necrosis factor signaling pathway,NF-kappa B(NF-κB)signaling pathway,peroxisome proliferators-activated receptors signaling pathway and so on.Conclusion:Modified Erzhiwan combined with epimedium may play the anti-atherosclerosis role by estrogen-like effect through attach estrogen receptor,inhibiting inflammation and improving insulin resistance,which may provide guidance for further experimental research.