基于网络药理学探讨银杏叶干预激素性股骨头坏死的作用机制

Exploring the intervention mechanism of Ginkgo biloba for steroid-induced necrosis of the femoral head based on network pharmacology

目的:基于网络药理学探讨银杏叶干预激素性股骨头坏死的作用机制。方法:利用TCMSP及PharmMapper数据库预测银杏叶活性成分及作用靶点,运用Genecards和OMIM数据库检索与激素性股骨头坏死相关的疾病靶点。使用Cytoscape 3.6.1构建蛋白质-蛋白质相互作用网络图,通过STRING数据库对银杏叶干预激素性股骨头坏死的靶点进行核心靶点分析、模块化分析、GO富集分析和KEGG通路分析。结果:本研究共筛选得到16种银杏叶活性成分及547个靶点,其中与激素性股骨头坏死相关的靶点为133个。通过PPI网络拓扑分析,证明TP53、AKT1、IL6、VEGFA、MAPK1、JUN、MAPK8、EGFR、EGF、MYC为核心靶点。GO模块化分析表明这些核心靶点主要与细胞凋亡、血管新生相关。GO富集分析了核心靶点参与的生物学过程、细胞定位及分子功能。KEGG富集分析靶点主要参与的分子信号通路,其中PI3K/AKT信号通路相关性最高。结论:银杏叶通过多组分、多靶点和多途径协同干预激素性股骨头坏死,为后续细胞实验及动物实验提供理论依据及参考。

AIM:To explore the mechanism of Ginkgo biloba in the treatment of steroid-induced osteonecrosis of the femoral head based on network pharmacology.METHODS:The active ingredients and targets of Ginkgo biloba were predicted by the TCMSP,ADME,and PharmMapper databases.The disease targets related to steroid-induced osteonecrosis of the femoral head were searched by the GeneCards and OMIM databases.Cytoscape 3.6.1 was used to construct a protein-protein interaction network.The core target analysis,modular analysis,GO enrichment analysis,and KEGG pathway analysis of the targets of Ginkgo biloba in the intervention of steroid-induced osteonecrosis of the femoral head were performed by the STRING database.RESULTS:In this study,a total of 16 active ingredients of Ginkgo biloba and 547 targets were screened,of which 133 targets were related to steroid-induced femoral head necrosis.By PPI network topology analysis,TP53,AKT1,IL6,VEGFA,MAPK1,JUN,MAPK8,EGFR,EGF,and MYC were identified as the core targets.GO modularization analysis showed that these core targets were mainly related to apoptosis and angiogenesis.GO enrichment analysis was used to analyze the biological processes,cellular localization,and molecular functions of the core targets.KEGG enrichment analysis showed that the targets were mainly involved in molecular signaling pathways,among which the PI3K/AKT signaling pathway was the most relevant.CONCLUSION:Ginkgo biloba can inhibit steroid-induced osteonecrosis of the femoral head through multiple components,targets,and pathways,which provides the theoretical basis and reference for subsequent cell and animal experiments.