[关键词]
[摘要]
【目的】探讨补肾强筋胶囊治疗骨质疏松症的分子机制。【方法】利用TCMSP、HERB、PubChem、Swiss 等数据库收集补 肾强筋胶囊的活性成分和潜在靶点。通过OMIM、GeneCards、DrugBank、TTD 等数据库检索骨质疏松症的相关靶点。通过韦 恩图得到药物靶点与疾病靶点的交集。通过Cytoscape 软件进行“药物-成分-靶点”网络构建及分析,利用STRING 数据库、 Cytoscape 软件绘制蛋白-蛋白相互作用(PPI)网络图及进行网络拓扑学分析,将共同靶点输入DAVID 数据库中进行基因本体 (GO)及京都基因与基因组百科全书(KEGG)通路富集分析。利用Auto Dock Vina 软件进行分子对接,用Pymol 软件进行可视 化展示。【结果】筛选出补肾强筋胶囊与骨质疏松症相关的68 个药效成分,包括山柰酚、β-谷甾醇、豆甾醇、槲皮素、柚皮 素、木犀草素等。PPI 网络拓扑分析得到关键靶点25 个,包括AKT1、IL6、TP53、JUN、SRC、BCL2 等。GO 功能富集分析 结果得到生物学过程(BP)331 项、细胞组分(CC)32 项、分子功能(MF)62 项。KEGG 通路富集分析结果得到相关信号通路153 条。 分子对接结果显示选取的靶点和成分均有较好的结合活性。【结论】补肾强筋胶囊可能是通过山柰酚、柚皮素、木犀草素、 槲皮素等活性成分,作用于SRC、BCL2、AKT1、IL6 等靶点调节多条信号通路发挥抑制细胞死亡、调节炎症免疫应答、抗 氧化应激等作用治疗骨质疏松症。
[Key word]
[Abstract]
Objective To investigate the molecular mechanism of Bushen Qiangjin Capsules in the treatment of osteoporosis. Methods The active components and potential targets of Bushen Qiangjin Capsules were collected using databases such as TCMSP,HERB,PubChem,and SwissTargetPrediction. Osteoporosis-related targets were retrieved from OMIM,GeneCards,DrugBank,and TTD. The overlapping targets between drug and disease were identified using a Venn diagram. The“drug-component-target”network was constructed and analyzed using Cytoscape software. A protein-protein interaction(PPI)network was constructed using the STRING database and Cytoscape,followed by network topology analysis. The common targets were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses using the DAVID database. Molecular docking was performed using AutoDock Vina,and the results were visualized with Pymol software. Results A total of 68 active components of Bushen Qiangjin Capsules associated with osteoporosis were screened out,including kaempferol,β-sitosterol,stigmasterol,quercetin,naringenin,and luteolin. PPI network topology analysis identified 25 key targets,such as AKT1,IL6,TP53,JUN,SRC,and BCL2. GO enrichment analysis yielded 331 biological process(BP)terms,32 cellular component(CC)terms,and 62 molecular function(MF) terms. KEGG pathway enrichment analysis identified 153 related signaling pathways. Molecular docking results indicated that the selected targets and components exhibited good binding affinities. Conclusion Bushen Qiangjin Capsules probably exert their therapeutic effects on osteoporosis by acting on targets such as SRC,BCL2,AKT1, and IL6 through its active components including kaempferol,naringenin,luteolin,and quercetin. It modulates multiple signaling pathways to inhibit cell death,regulate inflammatory immune responses,and counteract oxidative stress.
[中图分类号]
R285
[基金项目]
国家自然科学基金青年科学基金项目(编号:82405428);东莞市谭志超医学领军人才引进培养项目(东卫涵【2024】47 号文); 李征东莞市名中医传承工作室资助项目