摘要
目的:运用网络药理学的研究方法分析山慈菇–夏枯草治疗乳腺增生的潜在作用靶点和机制。方法:使用中药系统药理学数据库与分析平台(TCMSP)筛选山慈菇–夏枯草的有效活性成分及其对应的作用靶点,利用人类基因卡片数据库(GeneCards)、人类孟德尔遗传在线数据库(OMIM)检索获得乳腺增生疾病靶点。将药物作用靶点和疾病靶点取交集,并绘制韦恩图。分别运用Cytoscape 3.9.2软件和STRING数据库构建“药物有效成分–作用靶点”网络图和蛋白质–蛋白质相互作用网络图。应用R软件对交集基因进行基因本体论(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,运用AutoDock 1.5.6软件进行分子对接,PyMOL 3.0.3软件进行可视化分析。结果:共获得中药有效成分13种、有效活性成分靶点193个、疾病靶点5088个,药物–疾病共同靶点162个。通过蛋白质–蛋白质相互作用网络分析获得44个核心靶点。主要有效成分为槲皮素、β–谷甾醇、豆甾醇、木犀草素、2–甲氧基–9,10–二氢菲–4,5–二醇等,作用于丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Protein Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素(Interleukin,IL)–6、肿瘤蛋白p53(Tumor Protein p53,TP53)等核心靶点,通过调控等晚期糖基化终末产物(Advanced Glycosylation End Product,AGE)–AGE受体(Receptor of AGE,RAGE)信号通路、TNF信号通路、IL–17信号通路等提高细胞应对氧化应激能力、调节激素水平、抑制血管生成、抗炎性反应等治疗乳腺增生。分子对接显示,主要有效成分与疾病靶点具有较好的结合能力。结论:山慈菇–夏枯草通过多成分、多靶点、多通路治疗乳腺增生,本研究为临床治疗和实验探索提供了理论依据和参考。
Objective:Network pharmacology research method was used to analyze the potential targets and action mechanisms of Shancigu(Pseudobulbus Cremastrae seu Pleiones)-Xiakucao(Prunellae Spica)in the the treatment of breast hyperplasia.Methods:The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)was employed to retrieve the active constituents of Shancigu-Xiakucao and their respective targets.The GeneCards and OMIM databases were utilized to obtain the targets associated with breast hyperplasia.The intersection of potential targets of the medicines and disease was taken to drawn a Venny diagram that visually represented the common targets.Cytoscape 3.9.2 software and STRING database were employed to construct the active ingredients-targets network diagram and protein-protein interaction network diagram,respectively.Furthermore,R software was utilized to perform Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the intersecting genes.The AutoDock 1.5.6 software was used for molecular docking,and PyMOL 3.0.3 software was used for visual analysis.Results:The study successfully identified 13 active ingredients of Chinese medicines,193 corresponding targets,5088 disease targets associated with breast hyperplasia,and 162 medicine-disease common targets.A total of 44 core targets were obtained from the PPI network analysis.The main active ingredients included quercetin,β-sitosterol,stigmasterol,luteolin,and 2-methoxy-9,10-dihydrophenanthrene-4,5-diol,etc.,which acted on core targets such as AKT1,TNF,IL-6,and TP53 by regulating AGE-RAGE signaling pathway,TNF signaling pathway,as well as IL-17 signaling pathway to enhance cellular resistance to oxidative stress,regulate hormonal levels,inhibit angiogenesis,and inhibit inflammatory,thereby treating breast hyperplasia.The molecular docking results showed that the main active components had good binding ability with the targets.Conclusion:Shancigu-Xiakucao could treat breast hyperplasia through multiple components,targets and pathways,providing a theoretical basis and reference for clinical treatment and experimental exploration.
出处
《中医临床研究》
2025年第8期1-8,共8页
Clinical Journal Of Chinese Medicine
基金
浙江省中医药科技计划项目(2024ZL379)。
关键词
网络药理学
山慈菇–夏枯草
乳腺增生
Network pharmacology
Shancigu-Xiakucao
Breast hyperplasia
