[关键词]
[摘要]
目的 运用网络药理学及分子对接技术揭示黄芪在干预骨骼肌萎缩过程中的作用机理。方法 借助中药 系统药理学数据库与分析平台(TCMSP)及中药成分血清药代动力学数据库(DCABM-TCM),筛选出黄芪的有效 活性组分,并预测其潜在作用靶标;通过 GeneCards 和 OMIM 数据库预测与骨骼肌萎缩关联的靶基因,并利用 Uniprot 数据库完成基因名标准化;通过绘制 Venn 图获得黄芪与骨骼肌萎缩共同的作用靶点基因;利用 Cytoscape 工具绘制黄芪-活性成分-靶基因网络图,通过 String 数据库建立靶点蛋白相互作用(PPI)网络;借助 DAVID 数据库实施基因本体(GO)功能富集与基因组百科全书(KEGG)通路富集分析,明确黄芪影响骨骼肌萎 缩的关键信号传导途径;采用 Autodocktools 软件分析活性成分与核心靶点,并进行分子对接。结果 网络药 理学分析表明,黄芪中共筛选出 18 种关键化合物及 206 个潜在靶点;骨骼肌萎缩对应的疾病靶点有 452 个, 黄芪和骨骼肌萎缩共有 23 个交集靶点,获得 AKT1、TP53、PPARG、SLC2A4、CAV1、PTEN、AR、IL6、TNF 和 ESR1 等 10 个 PPI 网络核心分子;富集分析揭示,黄芪或可通过调控 75 条信号通路(如 IRS-1/PI3K/Akt 通 路、RAS/MAPK 通路)来介入骨骼肌萎缩过程,这些通路与胰岛素抵抗、肿瘤发展等生理病理活动紧密相关; 分子对接结果提示,黄芪提取物如槲皮素、芒柄花素等能与 TP53、AR、PPARG 等核心靶点特异性结合。结 论 黄芪治疗骨骼肌萎缩的作用可能与减少细胞凋亡,减轻炎症反应,调整自噬过程及促进细胞增殖分化等 有关。
[Key word]
[Abstract]
Objective To elucidate the mechanism of Astragali Radix in intervening skeletal muscle atrophy by using network pharmacology and molecular docking techniques. Methods Active components of Astragali Radix were screened through using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Database of Chinese Active Components' Blood Metabolites-Traditional Chinese Medicine (DCABMTCM), and their potential targets were predicted. Disease-related targets of skeletal muscle atrophy were predicted through GeneCards,OMIM,and gene names were standardized by using the Uniprot database. Venn diagrams were constructed to identify common targets between Astragali Radix and skeletal muscle atrophy. The Astragali Radix-active components-target genes network was visualized by using Cytoscape,and protein-protein interaction (PPI) networks were established through using the String database. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by using the DAVID database to identify the key signaling pathways through which Astragali Radix influences skeletal muscle atrophy. Molecular docking of active components with core targets was conducted using Autodocktools software. Results Network pharmacology analysis was used to identify 18 key compounds and 206 potential targets in Astragali Radix. A total of 452 diseaserelated targets for skeletal muscle atrophy were identified, with 23 overlapping targets between Astragali Radix and skeletal muscle atrophy. Ten core molecules in the PPI network,including AKT1,TP53,PPARG,SLC2A4,CAV1, PTEN,AR,IL6,TNF,and ESR1,were identified. Enrichment analysis revealed that Astragali Radix may intervene in skeletal muscle atrophy by regulating 75 signaling pathways,such as the IRS-1/PI3K/Akt pathway and RAS/MAPK pathway, which were closely related to physiological and pathological processes like insulin resistance and tumor development. Molecular docking results indicated that Astragali Radix extracts,such as quercetin and formononetin, could specifically bind to core targets like TP53,AR,and PPARG. Conclusion The therapeutic effects of Astragali Radix on skeletal muscle atrophy may be associated with reducing apoptosis, alleviating inflammation, modulating autophagy,and promoting cell proliferation and differentiation.
[中图分类号]
R285.5
[基金项目]
河北省自然科学基金项目(H2022209031);河北省中医药管理局科研计划项目(2024354)。