苦参对急性髓系白血病的潜在作用机制探究

Potential mechanism of Sophora flavescens against acute myeloid leukemia

目的通过网络药理学方法探究苦参对急性髓系白血病(acute myeloid leukemia,AML)的潜在作用机制。方法检索中药系统药理学数据库与分析平台,筛选出苦参有效活性成分及对应靶点,采用GeneCards数据库获得AML作用靶点,得到药物与疾病的交集靶点。利用Cytoscape3.7.2软件构建药物有效活性成分-靶点-疾病交互网络图。借助STRING数据库进行蛋白-蛋白相互作用(protein-protein interaction,PPI)网络构建,并用R软件进行分析,随后通过Cytoscape3.7.2软件绘制网络图,对交集靶点进行基因本体论生物学过程(gene ontology biological process,GO-BP)功能富集分析及京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果共筛选匹配出苦参有效活性成分45个,涉及靶点99个,AML相关靶点1549个,药物与疾病交集靶点64个,涉及有效成分22个。共筛选出62个PPI核心基因,GO功能富集分析显示靶点主要参与泛素样蛋白连接酶降解、活性半胱氨酸型内肽酶参与的凋亡过程、激活转录因子结合、核激素受体结合等生物过程。KEGG通路富集显示苦参主要参与了肿瘤的蛋白聚糖形成、磷脂酰肌醇-3-激酶/Akt激酶、肿瘤坏死因子及人体抑癌基因p53等信号通路。结论苦参治疗AML具有多成分、多靶点、多通路的作用特点,为进一步探究中医药对AML的治疗作用及相关机制提供参考。

Objective To explore the potential mechanism of active components of Sophora flavescens in acute myeloid leukemia(AML)based on network pharmacology.Methods We searched Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the effective active components and corresponding targets of Sophora flavescens were screened.The AML action targets were obtained by GeneCards database,and the intersection targets of drugs and diseases were obtained.Cytoscape3.7.2 software was used to construct the interaction network diagram of drug effective active components,targets and diseases.The protein-protein interaction(PPI)network is constructed with the help of STRING database,analyzed with R software,and then the network diagram is drawn with Cytoscape3.7.2 software,gene ontology biological process(GO-BP)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the intersection targets.Results A total of 45 active components of Sophora flavescens were screened and matched,including 99 targets,1549 AML related targets,64 drug disease intersection targets and 22 active components.62 PPI core genes were screened.GO-BP function enrichment analysis showed that the target was mainly involved in the degradation of ubiquitin protein ligase,the apoptosis process with cysteine endopeptidase activity,the binding of activating transcription factors,the binding of nuclear hormone receptors and other biological processes.KEGG pathway enrichment showed that Sophora flavescens was mainly involved in the formation of proteoglycan,phosphatidylinositol-3-kinase serine/Akt kinase,tumor necrosis factor and human tumor suppressor gene p53 in cancer.It also provided a certain reference for exploring the multi-channel and multi-target mechanism of Sophora flavescens in the treatment of AML.Conclusion Sophora flavescens has the characteristics of multi-component,multi-target and multi-channel in the treatment of AML,which also provides a certain reference for further exploring the therapeutic effect and related mechanism of traditional Chinese medicine on AML.