摘要
目的运用网络药理学的方法预测丹参对血小板聚集的主要活性成分、靶点及信号通路,探究其潜在的作用机制,以期开发新的抗血小板药物。方法通过TCMSP数据库筛选丹参的有效成分;输入Pharm Mapper数据库获得相应基因;检索GeneCards数据库获得血小板聚集的靶点基因;利用R语言3.6.3截取交集网络获得候选靶点;借助Cytoscape 3.7.2将“药物-化合物-靶点-疾病”网络可视化处理;在String平台上构建蛋白-蛋白相互作用(PPI)网络;利用DAVID数据库对候选靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路注释;潜在药效成分和关键靶点的分子对接由Autodock Vina 1.1.2实现。结果获得丹参中65个活性化合物、109个不重复的靶标信息、84个血小板聚集治疗靶点。GO功能富集得到GO条目1963个(P<0.05),其中生物过程(BP)条目1789个,细胞组分(CC)条目113个,分子功能(MF)条目61个;KEGG通路富集得到129条信号通路(P<0.05)。分子对接结果显示,丹参中的丹参酮ⅡA与G蛋白偶联受体(GPCRs)等靶点的亲和力强。结论丹参中的有效成分作用血小板聚集的机制与磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路的调控有关,丹参通过介导磷酸腺苷(ADP)诱导的C信号通路对血小板聚集具有较好的整合效应。
Objective To predict the main active components,targets and signaling pathways of Salviae miltiorrhiza on platelet aggregation by means of network pharmacology,and to explore its potential mechanism of action,so as to develop new antiplatelet drugs.Methods The effective components of Salviae miltiorrhiza were screened by TCMSP database.The corresponding genes were obtained by entering Pharm Mapper database.The target genes of platelet aggregation were obtained from Gene Cards database.The candidate targets were obtained by using R 3.6.3 intercept intersection network.With the help of Cytoscape3.7.2,the network of"drug-compound-target-disease"was visualized.The protein-protein interaction(PPI)network was built on String platform.The DAVID database was used for gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway annotation of the candidate targets.The molecular docking of potential medicinal ingredients and key targets was realized by Autodock Vina 1.1.2.Results 65 active compounds,109 non-repeated targets and 84 platelet aggregation targets were obtained from Salviae miltiorrhiza.There were 1963 GO items(P<0.05),among which 1789 were biological process(BP)items,113 were cell components(CC)items,and 61 were molecular function(MF)items.129 signal pathways were enriched by KEGG pathway(P<0.05).The results of molecular docking showed that tanshinoneⅡA in Salvia miltiorrhiza had a strong affinity with targets such as G-protein coupled receptor(GPCRs).Conclusion The mechanism of active components in Salviae miltiorrhiza acting on platelet aggregation is related to the regulation of phosphatidylinositol 3-kinase and protein kinase B(PI3K/Akt)signaling pathway,and Salviae miltiorrhiza has a good integration effect on platelet aggregation by mediating the C signal pathway induced by adenosine phosphate(ADP).
作者
霍苏
崔鹤蓉
顾昱昊
戴子琦
王亚欣
娄邵岩
戚蕊
项嘉伟
王鹏龙
马涛
雷海民
HUO Su;CUI Herong;GU Yuhao;DAI Ziqi;WANG Yaxin;LOU Shaoyan;QI Rui;XIANG Jiawei;WANG Penglong;MA Tao;LEI Haimin(School of Chinese Pharmacy,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《西北药学杂志》
2021年第4期586-595,共10页
Northwest Pharmaceutical Journal
基金
中央高校基金科研业务项目(编号:2019-JYB-TD005,BUCM-2019-JCRC002,2020-JYB-ZDGG-044)
中华中医药学会青年人才托举工程项目(编号:CACM-2018-QNRC2-B08)。
关键词
网络药理学
丹参
血小板聚集
作用机制
分子对接
network pharmacology
Salviae miltiorrhiza
platelet aggregation
mechanism of action
molecular docking
