摘要
目的通过网络药理学的方式检索黄芪治疗股骨头缺血性坏死的主要活性成分、作用靶点及通路,探索黄芪的潜在作用原理。方法通过TCMSP数据库平台筛选出黄芪的活性成分,并检索出其作用靶点,利用Uniprot、NCBI等数据库将其进行校正、规范。借用GeneCards及OMIM等数据库,以“股骨头缺血性坏死”英文全称:Ischemic necrosis of the femoral head为关键词获得股骨头缺血性坏死的疾病靶点,并将其进行规范整理。运用R语言系统将获得的黄芪高活性成分蛋白基因与INFH靶点基因进行韦恩分析,获取黄芪治疗INFH的交集靶点。借用Cytoscape3.7.2软件将黄芪与INFH的交集靶基因与黄芪高活性成分建立黄芪-活性成分-疾病-疾病靶点基因网络图,并利用插件计算相关网络特征值。将黄芪-疾病交集靶点基因导入到String数据库进行蛋白互作分析,构建蛋白(PPI)互作关系网络图,并通过KEGG通路富集分析及借用DAVID数据库将其进行GO功能富集分析预测其作用机制。结果筛选出黄芪20个活性成分,得到不重复的对应靶基因197个,治疗股骨头缺血性坏死的靶点69个。GO富集分析得到GO条目426项(P≤0.05),包括生物过程(BP)、细胞组分(CC)、分子功能(MF)分别有347、23、56项。KEGG通路富集分析共富集到78条信号通路(P≤0.05)。结论黄芪中的有效成分常春藤皂苷元、异鼠李素、刺芒柄花素、毛蕊异黄酮、山柰酚、槲皮素等能作用于IL6、TNF、IL10、AKT1、TP53、ESR1、STAT1等靶点通过调控RNA聚合酶II启动子的转录正调控、基因表达的正向调节、蛋白质磷酸化的正向调控、药物反应、炎症反应、负调控凋亡过程等及通过膀胱癌、疟疾、癌症、乙型肝炎、HIF-1信号通路、PI3K-Akt信号通路、TNF信号通路等多条相关信号通路共同协作治疗INFH疾病的作用。
Objective:To explore the potential action principle of Astragalus membranaceus by means of network pharmacology to search the main active ingredients,action targets and pathways of Astragalus in the treatment of avascular necrosis patients of femoral head.Methods:The active ingredients of Astragalus were screened by TCMSP database platform,and their targets were retrieved,and calibrated and standardized by Uniprot and NCBI.Through GeneCards and OMIM databases,the key words"ischemic necrosis of the femoral head"was searched to obtain the disease targets of ischemic necrosis of femoral head and to have them standardized.The R language system was used to conduct Wayne analysis between the gene of Astragalus high active component protein and the gene of INFH target to obtain the intersection target of Astragalus INFH treatment.By using Cytoscape3.7.2 software,the intersection target genes of Astragalus and INFH and the high active components of Astragalus were combined to establish the Astragalus-active components-disease-target gene network map,and the related network eigenvalues were calculated by using the plug-ins.Astragalus-disease intersection target genes were imported into String database for protein interaction analysis,and protein(PPI)interaction network map was constructed.The mechanism of action was predicted by KEGG pathway enrichment analysis and GO functional enrichment analysis by DAVID database.Results:20 active ingredients of Astragalus were screened,and 197 non-repetitive corresponding target genes were obtained,and 69 targets were identified for treatment of avascular necrosis of femoral head.426 GO items were obtained by GO enrichment analysis(P≤0.05),including 347 biological processes(BP),23 cell components(CC)and 56 molecular functions(MF),respectively.A total of 78 signaling pathways were enriched by KEGG pathway enrichment analysis(P≤0.05).Conclusion:The active ingredients of Astragalus,such as hederagenin,isorhamnetin,formononetin,calycosin,kaempferol and quercetin,can act on the targets of IL6,TNF,IL10,AKT1,TP53,ESR1 and STAT1 by regulating the positive transcriptional regulation of RNA polymerase II promoter,up-regulation of gene expression and positive regulation of protein phosphorylation,drug response,inflammatory response and negative regulation of apoptosis.The effect of co-treatment of INFH disease can be achieved through several related signaling pathways including bladder cancer,malaria,cancer,hepatitis B,HIF-1 signaling pathway,PI3K-Akt signaling pathway and TNF signaling pathway.
作者
王明明
程延
WANG Ming-ming;CHENG Yan(Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,China;Shaanxi Hospital of Traditional Chinese Medicine,Xi'an 710003,China)
出处
《云南中医中药杂志》
2023年第2期28-37,共10页
Yunnan Journal of Traditional Chinese Medicine and Materia Medica
基金
陕西省中医药管理局科研项目(SZY-KJCYC-2020-YJ)
陕西省中医药研究院/陕西省中医医院院级“苗圃培育计划”项目(2021-23)。
关键词
黄芪
网络药理学
股骨头缺血性坏死
通路
药物作用机制
Astragalus Membranaceus
Network Pharmacology
Avascular Necrosis of Femoral Head
Pathway
Mechanism of Drug Action
