摘要
目的:基于网络药理学的方法探讨半夏-陈皮-石菖蒲治疗缺血性卒中病的有效成分、靶点、网络通路以及潜在的分子机制。方法:引用中药系统药理学数据库与分析平台(TCMSP),将半夏-陈皮-石菖蒲药组的有效成分进行靶点预测,并在数据库内取得2D结构图,导进Phrammarpper数据库内获得半夏-陈皮-石菖蒲成分靶点。通过PharmGKb、GeneCard、DrugBank、Therapeutic Target Database四个数据库预测疾病的靶点。利用Venny 2.1制作韦恩图取得药物与疾病交集靶点。在STRING数据库内构建蛋白质-蛋白质相互作用网络。利用R语言和Cytoscape软件中CytoNCA APP取得核心靶点。通过R语言的BiocManager包和OrgDb包等和R Studio软件进行京都基因与基因组百科全书(KEGG)和基因本体论(GO)富集分析。利用Cytoscape软件,构成“药物-成分-靶点-通路”网络关系图。使用Autodock vina 1.1.2将半夏-陈皮-石菖蒲的核心成分与核心靶点进行分子对接。结果:获得药物的核心成分7个,分别为异戊烯基山柰酚、冈多酸、松柏苷、β-谷甾醇、桉脂素、山柰酚、黄芩苷。核心靶点20个,主要为丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、肿瘤蛋白p53(Tumor Protein p53,TP53)、半胱氨酸蛋白酶3(Caspase 3,CASP3)、丝裂原活化蛋白激酶3(Mitogen-Activated Protein Kinase 3,MAPK3)因子等。GO富集主要是活性氧依赖物质、细胞外刺激、脂多糖等的反应在突触前膜、膜筏和突触后膜等细胞组分上进行作用。KEGG富集主要有环磷酸腺苷(cyclic Adenosine Monophosphate,c AMP)、白细胞介素-17(Interleukin-17,IL-17)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等排名前30条信号通路。分子对接的结果也表明半夏、陈皮、石菖蒲的主要活性成分分别与选取的核心靶点CASP3、前列腺素氧化环化酶2(Prostaglandin-Endoperoxide Synthase2,PTGS2)、雌激素受体1(Estrogen Receptor 1,ESR1)等结合良好。结论:半夏-陈皮-石菖蒲具有多种有效成分、多个核心靶点、多条网络通路治疗缺血性卒中的特点,为治疗缺血性卒中提供了基础研究。
Objective:Based on network pharmacology,the mechanism of the treatment of acute ischemic stroke by Banxia(Rhizoma Pinelliae)-Chenpi(Pericarpium Citri Reticulatae)-Shichangpu(Rhizoma Acori Tatarinowii)is explored.Methods:Target prediction of the active components of Banxia-Chenpi-Shichangpu was carried out by TCMSP.2D structure map was obtained from the database and the target of Banxia-Chenpi-Shichangpu constituents was obtained from Phrammarpper database.The Target of the disease was predicted by PharmGKb,GeneCard,DrugBank and Therapeutic Target Database.Use Venny 2.1 to obtain drug and disease intersection targets.The protein interaction network was constructed in the STRING database.Core targets are obtained using R language and CytoNCA APP in Cytoscape software.KEGG and GO enrichment analysis were carried out through R language BiocManager package and OrgDb package and R Studio software.Using Cytoscape software,the network diagram of drug-component-target-pathway was constructed.Autodock vina 1.1.2 was used to dock the core components of Banxia-Chenpi-Shichangpu with the core target.Results:A total of 7 core components of the drug were obtained,including 8-isopentenyl-kaempferol,gondoic acid,coniferi,beta-sitostero,1R,3aS,4R,6aS-1,4-bis(3,4-dimethoxyphenyl)-1,3,3a,4,6,6ahexahydrofuro[4,3-c]furan,kaempferol,baicalin.There are 20 core targets,mainly AKT1,VEGFA,TP53,CASP3,MAPK3 factor,etc..GO enrichment is mainly caused by reactive oxygen species,extracellular stimuli,lipopolysaccharides and other reactions on the presynaptic membrane,membrane raft and postsynaptic membrane.KEGG enrichment mainly included the top 30 signaling pathways such as cAMP,IL-17 and TNF.The results of molecular docking also showed that the main active components of Banxia,Chenpi and Shichangpu were well combined with the selected core targets CASP3,PTGS2 and ESR1,respectively.Conclusion:Banxia-Chenpi-Shichangpu have the characteristics of multiple active components,multiple core targets and multiple network pathways in the treatment of ischemic stroke,which provides basic research for the treatment of ischemic stroke.
出处
《中医临床研究》
2023年第32期15-22,共8页
Clinical Journal Of Chinese Medicine
关键词
缺血性卒中
半夏-陈皮-石菖蒲
网络药理学
作用机制
分子对接
Acute ischemic stroke
Banxia-Chenpi-Shichangpu
Cyber pharmacology
Mechanism of action prediction
Molecular docking
