基于网络药理学及分子对接预测金雀花降血压的活性成分及作用机制

Prediction of antihypertensive active components and mechanism of Caragana Sin⁃ca based on network pharmacology and molecular docking

目的研究金雀花降血压的活性成分及作用机制。方法运用药理学技术平台Swiss ADME数据库选出金雀花中胃肠道吸收性较好,且类药性较高活性成分及其靶点,通过GeneCards数据库获取高血压相关靶点,将成分靶点和疾病靶点导入String数据库,构建金雀花成分靶点-高血压靶点互作网络,根据度值选出关键靶点。运用Metascape数据库对成分和疾病交集靶点进行基因本体(GO)和基因组百科全书(KEGG)通路富集分析。结果从金雀花中共筛选出8个降血压的活性成分:7,4'-二羟基黄酮、儿茶素、莞花素、金合欢素、槲皮素、樱花素、芹菜素、异鼠李素,与高血压靶点交集的132个靶点,以及55个关键靶点,如AKT1、VEGFA、MAPK3、EGFR、ESR1等靶点,主要集中在癌症通路、PI3K-Akt信号通路、Ras信号通路、MAPK信号通路等,并通过Autodock4软件进行分子对接,结果显示金雀花降压活性成分和核心靶点间有较强亲和力。结论金雀花可通过多途径、多靶点、多通路发挥降血压作用。

Objective To study the antihypertensive active components and mechanism of Caragana Sinca.Methods The Swiss ADME database,a technical platform of pharmacology,was used to select the active components and their targets of Caragana Sinca with good gastrointestinal absorption and high drug-likeness properties.Hypertension relat⁃ed targets were obtained through GeneCards database.The component target and disease target were imported into String database,so as to construct the interaction network of Caragana Sinca component target and hypertension target,and select the key targets according to the degree value.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Ge⁃nomes(KEGG)pathway enrichment analyses were performed on intersection targets of component and disease using the Metascape database.Results Eight antihypertensive active ingredients were screened from Caragana Sinca as fol⁃lows,7,4′-dihydroxyflavone,catechin,genkwanin,acacetin,quercetin,sakuratin,apigenin,isorhamnetin.132 targets inter⁃secting with hypertension targets,and 55 key targets,such as AKT1,VEGFA,MAPK3,EGFR,ESR1 and other targets,mainly in cancer pathway,PI3K-Akt signaling pathway,Ras signaling pathway,MAPK signaling pathway,etc.,and mo⁃lecular docking was carried out by Autodock 4 software.The results show there is a strong affinity between the antihy⁃pertensive active components of Caragana Sinca and the core target.Conclusion Caragana Sinca can exert its antihy⁃pertensive effect through multiple channels,targets and pathways.