基于网络药理学方法研究决明子活性成分治疗动脉粥样硬化的分子机制

Investigation into the Molecular Mechanisms of Active Ingredients of Cassiae Semen for Atherosclerosis Based on Network Pharmacology

目的应用网络药理学方法初步研究决明子抗动脉粥样硬化可能的有效活性成分和潜在靶点。方法通过TCMSP和SwissTargetPrediction数据库收集决明子主要活性成分及其潜在靶点,GeneCards、OMIM、TTD and DrugBank数据库挖掘AS相关靶点。利用R语言筛选药物与疾病间的交集靶点并绘制Venny图。应用String平台构建蛋白质相互作用网络,Cytoscape 3.7.2软件对PPI网络进行拓扑分析。基于DAVID网站完成富集分析,并利用R语言使结果可视化。利用Cytoscape 3.7.2软件建立决明子活性成分-靶点-通路网络,并分别生成14个活性成分作用网络。结果TCMSP数据库中共检索到aloe-emodin、Obtusin、quinizarin等决明子有效活性成分14个,有效活性成分潜在靶点542个。与挖掘到的574个动脉粥样硬化靶点取交集,共获得99个共同靶点。经Cytoscape 3.7.2软件拓扑分析后筛选出前20位核心靶点,包括SRC、JUN、MAPK8、MAPK14、CTNNB1等。GO富集分析共获得平滑肌细胞增殖的正调控、炎症反应等340个生物过程;KEGG通路富集分析得出104条通路,涉及VEGF、TNF和花生四烯酸代谢等通路。蒽醌类化合物主要作用于IL-17、TNF、VEGF、动脉粥样硬化流体剪切力和脂质代谢等靶点和通路;苯并吡喃酮类化合物主要作用于糖尿病性心肌病、动脉粥样硬化流体剪切力、VEGF、血小板活化、花生四烯酸代谢等靶点和通路。结论决明子治疗动脉粥样硬化具有多成分、多靶点、多通路的特点,主要通过影响炎症反应、氧化应激、血管新生和斑块稳定性等病理生理过程发挥治疗AS的作用。

Objective To shed light on the active ingredients and potential targets of Cassia semen against atherosclerosis(AS)based on network pharmacology.Methods The active ingredients and potential targets of Cassia semen were obtained from TCMSP and SwissTargetPrediction databases.Then,AS-related targets were screened using GeneCards,OMIM,TTD and DrugBank databases.The common targets of drugs and diseases were identified using R language and the Venn diagram was drawn.The protein-protein interaction(PPI)network was constructed using STRING platform,and the topological analysis was performed using Cytoscape 3.7.2 software.The enrichment analysis was accomplished using DAVID database,and the results were visualized using R language.Ultimately,the network of active ingredients-targets-pathways was constructed using Cytoscape 3.7.2 software,and 14 active ingredient action networks were generated.Results A total of 14 active ingredients(aloe-emodin,obtusin,quinizarin,etc.)and 542 related targets were sifted from TCMSP database.Furthermore,99 common targets were obtained by overlapping with 574 AS targets.The top 20 hub targets screened by topological analysis included SRC,JUN,MAPK8,MAPK14,CTNNB1,etc.Totally 340 biological processes such as positive regulation of smooth muscle cell proliferation and inflammatory reaction were identified by GO enrichment analysis.Moreover,104 pathways such as VEGF,TNF and arachidonic acid metabolism were revealed by KEGG pathway enrichment analysis.Anthraquinone compounds mainly act on targets and pathways such as IL-17,TNF,VEGF,atherosclerotic fluid shear force and lipid metabolism.Benzopyrone compounds mainly acted on diabetic cardiomyopathy,atherosclerotic fluid shear force,VEGF,platelet activation,arachidonic acid metabolism,and other targets and pathways.Conclusion The anti-atherosclerotic effects of Cassia semen are characterized by multi-component,multi-target and multi-pathway,and its mechanisms of action are mainly involved in pathophysiological processes such as inflammatory response,oxidative stress,angiogenesis and plaque stability.