摘要
目的:基于网络药理学联合基因表达综合数据库(Gene Expression Ominibus,GEO)及分子对接策略,通过数据挖掘和分析的研究方法探究荷丹胶囊治疗非酒精性脂肪性肝病(Non–alcoholic Fatty Liver Disease,NAFLD)的可能机制。方法:基于网络药理学整合中药活性成分靶点与NAFLD疾病靶点,构建蛋白质–蛋白质相互作用网络并挖掘功能模块。结合GEO中基因表达数据,进行差异分析与加权基因共表达网络分析。通过基因本体论(GO)/京都基因与基因组百科全书(KEGG)富集分析、基因集富集分析(Gene Set Enrichment Analysis,GSEA)及基因组变异分析(Gene Set Variation Analysis,GSVA)评估通路活性。采用关联规则挖掘、Cyto Hubba、K–近邻算法筛选核心靶点。最后通过分子对接与分子动力学模拟验证关键活性成分与靶点结合性质。结果:共鉴定出83种活性成分与443个潜在靶点。蛋白质–蛋白质相互作用网络揭示MEgrey模块与NAFLD具有显著关联(P<0.05),聚焦126个基因。GO和KEGG富集分析主要涉及腺苷酸活化蛋白激酶(Adenosine Monophosphate Activated Protein Kinase,AMPK)、磷脂酰肌醇3激酶(Phosphatidylinositol 3–kinase,PI3K)–蛋白激酶B(Akt)及叉头转录因子O1(Forkhead Box Protein O1,Fox O1)信号通路。GSEA联合GSVA分析一致支持PI3K–Akt通路活性增强。通过关联规则与网络拓扑筛选出沉默信息调节因子1(Silencing Information Regulator 1,SIRT1)、胰岛素样生长因子–1(Insulin–like Growth Factor–1,IGF1)、周期蛋白D1(Cyclin D1,CCND1)、周期素依赖性激酶抑制因子1A(Cyclin–Dependent Kinase Inhibitor 1A,CDKN1A)为核心靶点。分子对接显示补骨脂异黄酮醛与IGF1的结合能最低,分子动力学模拟验证复合物结构稳定。结论:本研究构建了“中药–靶点–通路–疾病”多层次分析框架,系统揭示了荷丹胶囊治疗NAFLD的可能分子机制,为其临床应用和新药开发提供了理论依据。
Objective:To investigate the potential mechanisms of the Hedan capsule(荷丹胶囊)in the treatment of non-alcoholic fatty liver disease(NAFLD)through data mining and analytical research methods based on network pharmacology combined with the GEO database and molecular docking strategies.Methods:Potential targets of Chinese medicinal material active components and NAFLD-related disease targets were integrated via network pharmacology to construct a protein-protein interaction network and identify functional modules.Based on the gene expression data in the GEO,differential expression analysis and weighted gene co-expression network analysis were performed.Pathway activities were assessed by GO/KEGG enrichment analysis,GSEA,and GSVA.Core targets were screened by association rule mining,CytoHubba,and the KNN algorithm.Finally,molecular docking and molecular dynamics simulations were performed to validate the binding properties of key components and targets.Results:A total of 83 active components and 443 potential targets were identified.The protein-protein interaction network revealed that the MEgrey module was significantly associated with NAFLD(P<0.05),highlighting 126 genes.The GO/KEGG enrichment analyses mainly involved AMPK,PI3K-Akt,and FoxO1 signaling pathways.The GSEA/GSVA consistently indicated enhanced PI3K-Akt pathway activity.Association rules and network topology identified SIRT1,IGF1,CCND1,and CDKN1A as core targets.Molecular docking demonstrated that corylinal exhibited the lowest binding energy with IGF1.Molecular dynamics simulations confirmed the structural stability of the complexes.Conclusion:This study establishes a multi-level analytical framework of“Chinese medicinal material-target-signaling pathway-disease”,systematically elucidating the underlying molecular mechanisms of the Hedan capsule in the treatment of NAFLD,which provides a theoretical foundation for its clinical application and novel medicine development.
出处
《中医临床研究》
2025年第29期110-123,共14页
Clinical Journal Of Chinese Medicine
基金
福建省卫生健康中青年骨干人才培养项目(2022GGB020)
厦门市扶持中医药发展专项项目(XWZY-2023-0610)。
