[关键词]
[摘要]
目的 利用网络药理学和分子对接技术,研究路路通Liquidambaris Fructus治疗类风湿关节炎的分子机制。方法 通过TCMSP数据库确定路路通的活性成分和潜在作用靶点。利用GeneCards、OMIM、DisGeNET数据库检索类风湿关节炎的相关靶点。使用Venny 2.1绘制韦恩图,确定交集靶点。基于STRING数据库,使用Cytoscape 3.10软件构建“药物–活性成分–潜在靶点–疾病”网络图,并通过拓扑分析筛选核心靶点。利用DAVID数据库进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。通过Autodock软件进行分子对接实验。结果 筛选出松脂素、β-谷甾醇、谷甾醇、异斯他丁环氧4个活性成分,169个潜在靶点。确定了114个与类风湿关节炎相关的交集靶点。构建了“中药–成分–靶点–疾病”网络,筛选出溶质载体家族6成员3(SLC6A3)、11-β-羟基类固醇脱氢酶1(HSD11B1)等核心靶点。GO与KEGG富集分析揭示了多个生物学过程和信号通路,如神经活性配体-受体相互作用、钙信号通路等。分子对接验证了活性成分与核心靶点之间的相互作用。结论 路路通可能通过调节类风湿关节炎相关的关键靶点(SLC6A3、HSD11B1等)和信号通路,发挥抗炎和免疫调节作用,为类风湿关节炎的临床治疗提供了新的分子层面的证据。
[Key word]
[Abstract]
Objective To study the molecular mechanism of Liquidambaris Fructus in treatment of rheumatoid arthritis by utilizing network pharmacology and molecular docking technology. Methods The active components and potential targets of action of Liquidambaris Fructus were identified by TCMSP databases. GeneCards, OMIM, and DisGeNET databases were utilized to search for relevant targets of rheumatoid arthritis. Venn diagrams were plotted using Venny 2.1 to identify intersecting targets. Based on the STRING database, Cytoscape 3.10 software was used to construct a network diagram of “drug-active ingredient-potential target-disease”, and the core targets were screened by topological analysis. GO enrichment analysis and KEGG pathway enrichment analysis were performed using DAVID database. Molecular docking experiments were performed by Autodock software.Results Including pinosylvin, β-sitosterol, sitosterol, and isostatin epoxide, and 169 potential targets were screened. The 114 intersecting targets related to rheumatoid arthritis were identified. The network of “drug-active ingredient-potential target-disease” was constructed, and 54 core targets were screened, such as SLC6A3, HSD11B1, etc. GO and KEGG enrichment analysis revealed a number of biological processes and signaling pathways. GO and KEGG enrichment analysis revealed multiple biological processes and signaling pathways, such as neuroactive ligand-receptor interactions, calcium signaling pathway, etc. Molecular docking verified the interactions between active ingredients and core targets. Conclusion Liquidambaris Fructus may exert anti-inflammatory and immunomodulatory effects by modulating rheumatoid arthritis -related key targets (SLC6A3, HSD11B1, etc.) and signaling pathways, providing new evidence at the molecular level for the clinical treatment of rheumatoid arthritis.
[中图分类号]
R285
[基金项目]
黑龙江省中医药科研项目(ZHY2023-099)