摘要
目的:本研究旨在综合运用网络药理学与分子对接技术系统探讨“黄精–熟地黄”药对治疗高脂血症的潜在作用机制,为该药对的临床应用及药物开发提供理论依据。方法:通过TCMSP数据库筛选黄精与熟地黄的活性成分及其对应靶点,利用DrugBank、PharmGKB、Genecards等多个疾病靶点数据库收集与高脂血症相关的靶点基因,运用STRING Version 11.5数据库构建蛋白质–蛋白质相互作用网络,并借助Cytoscape 3.9.1软件绘制“药物–活性成分–靶点”调控网络。基于R语言平台与DAVID数据库对关键靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析(设定P≤0.05为显著水平)。最后利用AutoDock Vina软件对核心活性成分与关键靶点进行分子对接验证,评估其结合能力与稳定性。结果:共筛选到“黄精–熟地黄”药对中14个活性成分及87个高脂血症相关靶点,蛋白质–蛋白质相互作用网络分析提示药物与疾病55个交集靶点之间存在密切相互作用;富集分析结果显示,这些靶点显著富集于1134个GO生物过程和117条KEGG信号通路;分子对接结果表明,黄芩素等主要活性成分与基质金属蛋白酶(Matrix Metalloproteinase,MMP)9、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)等核心靶点蛋白具有较强的结合亲和力,结合构象稳定。结论:“黄精–熟地黄”药对可能通过多成分、多靶点、多通路的方式协同作用,主要参与调节脂质代谢过程、抑制炎性反应和调控细胞增殖与凋亡等生物过程,从而发挥治疗高脂血症的效应。本研究初步揭示了其潜在分子机制,为两药联合炮制研究和药物开发提供了参考依据。
Objective:To research the potential mechanisms of Huang Jing(Rhizoma Polygonati)and Shu Di Huang(Radix Rehmanniae Preparata)couplet medicinals in the treatment of hyperlipidemia through network pharmacology and molecular docking.Methods:The TCMSP database was used for screening the active components of Huang Jing and Shu Di Huang as well as their potential targets,while Genecards,OMIM,PharmGKB,Drugbank and other databases were accessed to obtain data about hyperlipidemia related target genes.The protein-protein interaction(PPI)network was constructed using STRING Version 11.5 database,and the“drug-active components-target”regulatory network was drawn with the help of Cytoscape 3.9.1 software.Based on R language platform and DAVID database,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for key targets(set P≤0.05 as significant level).Finally,AutoDock Vina software was used to verify the molecular docking between the core active components and key targets,and evaluate their binding ability and stability.Results:A total of 14 active components and 87 hyperlipidemia related targets in the“Huang Jing and Shu Di Huang”couplet medicinals were screened.PPI network analysis suggested that there were close interactions between these targets.The enrichment analysis results showed that these targets were significantly enriched in 1134 GO biological processes and 117 KEGG signaling pathways.Molecular docking results showed that baicalein and other major active components had strong binding affinity with core target proteins such as MMP9 and AKT1,and the binding conformation was stable.Conclusion:The couplet medininals of“Huang Jing and Shu Di Huang”may act synergistically through multi-component,multi-target and multi-pathways,and mainly participate in the regulation of lipid metabolism process,inhibition of inflammatory response,regulation of cell proliferation and apoptosis and other biological processes,so as to exert the effect of treating hyperlipidemia.This study initially revealed the underlying molecular mechanism,and provided a reference for the joint processing research and drug development of the couplet medininals.
出处
《中医临床研究》
2025年第29期97-105,共9页
Clinical Journal Of Chinese Medicine
基金
贵州省中药炮制技术传承基地建设项目(黔中医药函[2024]22号)
2023年度贵州省中医药、民族医药重点学科建设学科[QZYYZDXK(JS)-2023-04]
贵州省科技计划项目(黔科合基础-ZK[2022]一般504)。
关键词
网络药理学
高脂血症
黄精
熟地黄
分子对接
Network pharmacology
Hyperlipidemia
Huang Jing
Shu Di Huang
Molecular docking
