基于网络药理学探究附子温阳作用机制

Exploring yang-warming mechanism of aconite based on network pharmacology

目的应用网络药理方法,探讨附子温阳作用的可能机制。方法以心力衰竭和类风湿性关节炎为疾病模型,应用中药系统药理数据库和分析平台,根据口服生物利用度(OB)和药物相似度(DL)来筛选附子的活性成分,并预测出相应靶标;经人类表型术语集(HPO)数据库检索心力衰竭和类风湿性关节炎的疾病靶标;然后在蛋白质相互作用数据库(STRING)分别构建"附子成分-潜在靶标-心力衰竭"和"附子成分-潜在靶标-类风湿性关节炎"网络,通过Cytoscape软件将上述网络可视化,再根据节点介度、紧密度和连接度分别得到上述两个疾病网络的关键节点,借助GATHER数据库平台对关键节点进行京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)的基因功能富集分析。结果 "附子成分-潜在靶标-心力衰竭"网络包含146个节点,关键节点53个;"附子成分-潜在靶标-类风湿性关节炎"网络包含26个节点,关键节点10个;附子与心力衰竭相关的KEGG通路2条,与类风湿性关节炎相关的KEGG通路3条;两种疾病的共同通路为前列腺素(Prostaglandins,PGs)代谢通路和白三烯(Leukotrienes,LTs)代谢通路。结论经网络药理学测算,附子温阳的作用机制可能与其影响机体的PGs、LTs代谢通路有关。

Objective To explore the possible mechanism of aconite for the warming yang effect by using network pharmacology method.Methods With heart failure and rheumatoid arthritis as disease models,the TCMSP database was used to select the aconite active ingredients and the corresponding targets by bioavailability(OB) and drug similarity(DL).At the same time,heart failure and rheumatoid arthritis diseases targets were searched by using the HPO(The Human Phenotype Ontology) database.And then "aconite component-potential target-heart failure" and "aconite component-potential target-rheumatoid arthritis" networks were constructed through STRING database.The above networks were visualized by using Cytoscape software.According to the parameters of the node degree,the closeness and link degree of node,the key nodes of the two disease networks were obtained.Finally,the key nodes were analyzed by using the GATHER database platform for KEGG(Kyoto Encyclopedia of Genes and Genomes) gene function enrichment analysis.Results The network of "aconite component-potential target-heart failure" included 146 nodes and 53 key nodes.The network of"aconite component-potential target-rheumatoid arthritis" contained 26 nodes and 10 key nodes.Two KEGG pathways were related to heart failure and three KEGG pathways were related to rheumatoid arthritis.The prostaglandin(PGs) and leukotriene(PGs) metabolic pathways were the same pathways of two diseases.Conclusion According to the results of network pharmacology research,the yang-warming mechanism of aconite may be related to the PGs and LTs metabolic pathways.