摘要
目的利用网络药理学、分子对接技术,筛选并分析丹参治疗缺血性脑卒中(CIS)的关键化合物、作用靶点、生物学功能及信号通路,阐述其可能的作用机制。方法使用TCMSP数据库检索丹参的活性成分及作用靶点,在GeneCards、NCBI和OMIM数据库中获取CIS的靶点,并将药物和疾病交集后的靶点输入STRING数据库,构建蛋白质相互作用网络,利用Cytoscape 3.7.2软件构建药物-化合物-作用靶点-疾病网络。通过Bioconductor进行GO功能富集和KEGG通路分析。采用AutoDock Tools 1.5.6、AutoDock vina 1.1.2将得到的关键活性成分和核心靶点进行分子对接,运用Pymol和Ligplot软件对结果进行可视化。结果从丹参中共筛选出65个活性成分和108个对应靶点,以及CIS交集后获得靶点87个,其中度值大于50的靶点有6个,包括AKT1、IL6、FOS、VEGFA、MAPK1、EGFR,即本研究的核心靶点。GO功能富集分析得到GO条目124个(P<0.05),KEGG通路富集分析筛出134条信号通路(P<0.05),以PI3K-AKT信号通路所占靶点数目最多。构建的药物-化合物-作用靶点-疾病网络显示,木犀草素、丹参酮ⅡA等活性化合物在整个网络中发挥着关键作用;分子对接结果显示,木犀草素、丹参酮ⅡA与6个核心靶蛋白均具有较好的亲和力(结合能远小于-5 kJ/mol)。结论丹参的主要活性化合物,包括木犀草素、丹参酮ⅡA等,可作用于AKT1、IL6、FOS、VEGFA、MAPK1、EGFR等核心靶点,共同参与调节PI3K-AKT等多条信号通路,发挥抑制细胞凋亡、抗炎、神经保护等作用,可能是丹参治疗CIS的潜在机制。
Objective To screen the key compounds,targets,biological functions and signal pathways of Salviae miltiorrhizae in treatment of cerebral ischemic stroke by using network pharmacology and molecular docking techniques,and to analyze the possible mechanism of action.Methods TCMSP database was emaployed to search for the active ingredients and targets of Salviae miltiorrhizae,as well as the targets of CIS were obtained in GeneCards,NCBI and OMIM database.Then drug targets and disease targets were overlapped,and put into STRING database to establish a protein interaction network.Moreover,drug-compound-targetdisease network was constructed and GO function and KEGG pathway enrichment analysis were carried out in Bioconductor.With the aid of AutoDock Tools 1.5.6 and AutoDock vina 1.1.2,the key active ingredients and core targets were docked at molecular level,and the results were visualized by using Pymol and Ligplot software.Results A total of 65 active ingredients and 108 targets were selected out from Salviae miltiorrhizae,and 2558 targets were collected related to CIS.After intersection,87 targets were obtained,among which the degree value of 6 targets was greater than 50,including AKT1,IL6,FOS,VEGFA,MAPK1,EGFR,as the core targets of this study.A total of 124 GO entries and 134 signal pathways were identified,with the PI3 K/AKT signal pathway occupying the largest number of targets.The results showed that luteolin and tanshinoneⅡAplayed a key role in the drug-compoundtarget-disease network and well connected to six core targets(binding energy is much less than-5 kJ/mol).Conclusion The main active compounds of Salviae miltiorrhizae,such as luteolin,tanshinoneⅡA,could target for AKT1,IL6,FOS,VEGFA,MAPK1,EGFR,and participated in the regulation of PI3 K/AKT signaling pathway and many other pathways,responsible for anti-apoptosis,antiinflammatory,neuroprotection and other biological functions,that may be potential mechanisms of Salvia miltiorrhiza in treatment of CIS.
作者
王哲义
孙怿泽
刘碧原
樊竹
王春国
田金洲
卢涛
WANG Zheyi;SUN Yize;LIU Biyuan;FAN Zhu;WANG Chunguo;TIAN Jinzhou;LU Tao(Beijing University of Chinese Medicine,Beijing 100029,China;School of Life Science,Beijing University of Chinese Medicine,Beijing 100029,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100010,China;Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《药物评价研究》
CAS
2021年第2期344-355,共12页
Drug Evaluation Research
基金
北京市双一流高层次人才科研经费项目(1000041510053)。
