甘草苷治疗抑郁症和糖尿病共病的网络药理学作用机制研究

An exploration on mechanisms of “treating different diseases with same method” of liquiritin in treating depression and diabetes based on network pharmacology

本研究旨在采用网络药理学的方法探究甘草苷治疗抑郁症和糖尿病的药理作用机制。首先应用PharmMapper、SEA、SIB等数据库查找出与甘草苷有关的作用靶点,登陆GeneCards、DrugBank数据库分别查找出文献中已报道的与抑郁症和糖尿病有关的靶点,将疾病靶点分别与甘草苷相关作用靶点进行映射,筛选出与甘草苷治疗抑郁症和糖尿病有关的潜在作用靶点,采用Cytoscape 3.6.0软件构建成分-靶点-疾病网络并进行可视化分析。然后通过生物学信息注释数据库DAVID对抑郁症与糖尿病相同潜在靶点进行GO富集分析以及KEGG代谢通路富集分析,使用BITOLA系统搜索与抑郁症和糖尿病“基因或基因产品”相关的所有中间概念,系统识别甘草苷治疗抑郁症和糖尿病相同靶点的部位归属。本研究筛选得到与甘草苷有关的靶点共312个,其中23个是甘草苷治疗抑郁症和糖尿病共同的潜在作用靶点,包括ESR1、HRAS、VEGFA、NOS3、PARP1、IGF1R等,主要通过调控PI3K-AKT信号通路、癌症信号通路、Ras信号通路发挥治疗抑郁症和糖尿病的作用。

To predict the action targets of liquiritin in treating depression and diabetes to understand the“component-target-pathways”using the network pharmacology method.The major targets of liquiritin were obtained by PharmMapper,SEA,SIB databases.The GeneCards and DrugBank were used to predict the related targets of depression and diabetes.Compared these targets with major targets of liquiritin to predict the potential targets of depression and diabetes.The network of“component-target-disease”was constructed and analyzed by using Cytoscape 3.6.0 software.The same target proteins related to depression and diabetes were analyzed by using Gene Ontology(GO)tool,and the action pathway of its target proteins was analyzed by using enrichment method.The BITOLA system was used to search all intermediate concepts relevant to the“gene or gene product”for depression and diabetes to filter the intermediate concepts.The network analysis results showed that 312 targets were involved in liquiritin and 23 potential targets were related to depression and diabetes mellitus,such as ESR1,HRAS,VEGFA,NOS3,PARP1,IGF1R,et al.The signaling pathway enrichment results showed that the main action proteins exerted its antidepressant and hypoglycemic function by regulating the PI3K-AKT,cancer,Ras and other signaling pathways.