唐古红景天干预肺动脉高压作用机制的网络药理学研究

Study of network pharmacology on the active mechanism of Rhodiola tangutica in the intervention of pulmonary hypertension

目的采用网络药理学方法探讨唐古红景天干预肺动脉高压的作用机制。方法以唐古红景天主要化学成分为研究对象,借助Swiss Target Prediction网络服务器预测各化合物作用靶点,结合GeneCards数据库获取的肺动脉高压相关靶点,获取各化合物的作用靶点;利用STRING数据库构建对应靶标蛋白的互作网络;借助R语言进行CO功能和KECG通路富集分析,并利用Cytoscape 3.6.1软件构建化合物-靶点-通路网络图。结果﹑本研究共筛选获得唐古红景天的有效化学成分14个,肺动脉高压潜在作用靶点38个,并建立了靶点蛋白的互作网络。GO、KECG通路富集分析结果显示,唐古红景天可能主要通过山奈酚、咖啡酸、檞皮素、红景天苷等活性成分,作用于TNF、AKT1、ECFR、PTGS2、SRC、MMP9、MAPK14、ESR1、HRAS等靶点,调节ErbB、AMPK、HIF-1、PI3K-Akt、JAK-STAT等信号通路发挥有效作用。并构建了化合物-靶点-通路网络图。结论筛选出唐古红景天干预肺动脉高压的具体化学成分有14个并具有明显的多靶点/多通路的作用特征;推测唐古红景天干预肺动脉高压的具体作用机制可能涉及到ErbB、AMPK、HIF-1、PI3K-Akt、JAK-STAT、IL-17、FoxO、Ras等信号通路。

ObjectiveTo explore the active mechanism of Rhodiola tangutica in the intervention of pulmonaryhypertension by means of network pharmacology.Methods Main chemical constituents of Rhodiola tangutica weretaken as the research object to predict the action targets of each compound by means of network server Swiss TargetPrediction.The action targets of each compound were obtained by combining the related targets of pulmonary hyper-tension obtained from database CeneCards.An interaction network corresponding to the target protein was construc-ted by using database STRING;the enrichment analysis of CO function and KECG pathway were analyzed by usingR language,and compound-target-pathway network diagram was constructed by using software Cytoscape 3.6.1.Results In this study,14 effective chemical constituents of Rhodiola tangutica and 38 potential targets of pulmonaryhypertension were screened,and the interaction network of target proteins was established.The results of the enrich-ment analysis of CO and KECC pathway showed that Rhodiola tangutica may act on TNF,AKT1,ECFR,PTCS2,SRC,MMP9,MAPK14,ESR1,HRAS and so on by means of active constituents such as Kaempferol,caffeic acid,quercetin and salidroside.Besides,it may regulate some signal pathways including ErbB,AMPK,HIF-1,PI3K-Aktand JAK-STAT.The network diagram of compound-target-pathway was constructed.Conclusions There are 14specific chemical constituents of Rhodiola tangutica in the intervention of pulmonary hypertension,and it has obvi-ous multi-target and multi-channel action characteristics.It is speculated that the specific active mechanism ofRhodiola tangutica in the intervention of pulmonary hypertension may involve ErbB,AMPK,HIF-1,PI3K-Akt,JAK-STAT,IL-17,FoxO,Ras and other signal pathways.