基于网络药理学探究黄芪-党参治疗骨髓增生异常综合征的作用机制

Exploring the action mechanism of astragalus-codonopsis on myelodysplastic syndrome based on network pharmacology

目的:采用网络药理学方法构建黄芪-党参活性成分-作用靶点网络,分析其作用通路,探究黄芪-党参治疗骨髓增生异常综合征的潜在作用机制。方法:通过中药系统药理学数据库与分析平台搜集黄芪、党参的主要活性成分,利用Uniprot、Swiss Target Prediction获取黄芪、党参活性成分对应的靶点基因;运用GeneCard、OMIM、Drugbank检索骨髓增生异常综合征的相关作用靶点,将黄芪-党参活性成分作用的靶点基因与疾病靶点取交集,可得黄芪-党参治疗骨髓增生异常综合征的有效作用靶点。通过Cytoscape 3.8.0软件构建活性成分-作用靶点蛋白网络图,并运用String数据库得到蛋白质-蛋白质相互作用网络图,应用DAVID数据库对相关作用靶点进行京都基因与基因组百科全书富集分析和基因本体论富集分析,结合相关文献分析归纳黄芪-党参治疗骨髓异常综合征的作用机制。结果:筛选获得黄芪活性成分28个,党参活性成分18个,相关作用靶点共638个,结果显示黄芪-党参可能通过肿瘤蛋白P53(Tumor Protein P53,TP53)、趋化因子受体4(C-X-C Motif Chemokine Receptor 4,CXCR4)、MYC原癌基因(MYC Proto-Oncogene,MYC)、RUNX家族转录因子1(RUNX Family Transcription Factor 1,RUNX1)等关键基因,参与JAK/STAT途径、Wnt信号通路等来发挥治疗骨髓增生异常综合征的作用。结论:本研究体现了黄芪-党参多成分-多靶点-多途径的作用特点,揭示了黄芪-党参治疗骨髓增生异常综合征可能的作用机制,可为中医药干预骨髓增生异常综合征的临床应用提供依据,为后续机制研究提供新思路和方法。

Objective:To construct a network of astragalus-codonopsis active ingredients-action targets based on network pharmacology,then analyze its pathways,in order to explore the potential mechanism of astragalus-codonopsis on myelodysplastic syndromes.Methods:The main active components of astragalus and codonopsis were collected through TCMSP database.The target genes corresponding to the active components of astragalus and codonopsis were obtained by Uniprot and Swiss Target Prediction software.The relevant action targets of MDS were retrieved in GeneCard,OMIM,and Drugbank databases.The intersections of target genes of astragalus-codonopsis active ingredients and disease targets were the effective targets of astragalus-codonopsis on MDS.The active ingredient-target protein network diagram was constructed by Cytoscape 3.8.0 software.The PPI network diagram was obtained by String database.The KEGG enrichment analysis and GO enrichment analysis of the relevant targets were performed by DAVID database.The action mechanism of astragalus-codonopsis on MDS was analyzed based on the related literature.Results:28 active components of astragalus and 18 active components of codonopsis were obtained.There were 638 relevant targets in total.The results showed that astragalus-codonopsis may participate in JAK/STAT pathway and Wnt signaling pathway through key genes such as TP53,CXCR4,MYC,and RUNX1 to play the role of treating MDS.Conclusion:This study reflects the multi-components,multi-targets,multi-pathway action characteristics of astragalus-codonopsis,reveals the possible mechanism of astragalus-codonopsis on MDS,can provide a basis for the clinical application of Chinese materia medica intervention on MDS,and provide new ideas and methods for further research.