基于网络药理学及分子对接的银杏叶治疗神经胶质瘤机制分析

Analysis on potential mechanisms of Ginkgo biloba leaf used in the treatment of glioma based on network pharmacology and molecular docking

目的基于网络药理学及分子对接探究银杏叶治疗神经胶质瘤的机制。方法运用TCMSP数据库获取银杏叶活性成分,利用ETCM、symMap,BindingDB数据库挖掘银杏叶活性成分对应的靶蛋白,通过DisGeNET、GeneCards、DrugBank数据库挖掘胶质瘤靶点基因信息,筛选获得共同靶点基因,采用Cytoscape 3.9.1绘制蛋白-蛋白互作网络图获得hub基因,进行通路富集分析,并构建银杏叶治疗神经胶质瘤的疾病-靶点-通路网络模型,采用AutoDock软件进行分子对接验证活性成分与靶点的结合性,通过TCGA和GTEx数据库获得低级别胶质瘤和胶质母细胞瘤的基因表达和临床数据,对核心靶点基因进行生物信息学分析。结果共挖掘到银杏叶活性成分和神经胶质瘤共同靶点基因197个,并获得hub基因。分子对接结果表明神经胶质瘤hub基因中STAT3、TNF、TP53、ACTB、VEGFA、GAPDH的靶蛋白均能与相关银杏叶活性成分产生高效结合。生物信息学分析表明核心靶点基因在神经胶质瘤中的表达均显著上调,并具有潜在诊断、预后预测和治疗价值。结论银杏叶可能通过槲皮素、木犀草素等主要活性成分作用于STAT3、TNF、TP53、VEGFA等核心靶点基因的蛋白,调控氧化应激、MEK/ERK、PI3K/AKT等信号通路在神经胶质瘤的治疗中发挥作用。

AIM To investigate the potential mechanism of Ginkgo biloba leaf based on network pharmacology.METHODS The active components of Ginkgo biloba leaf were collected by TCMSP database. The target proteins corresponding to active components were obtained by ETCM, symMap and BindingDB databases. The target genes of glioma were extracted from DisGeNET, GeneCards and DrugBank databases. Cytoscape 3.9.1 was used to map the proteinprotein interaction network and bioinformatics enrichment analysis of GO and KEGG was conducted. The disease-targetpathway network model of Ginkgo biloba leaf in glioma treatment was constructed. The molecular docking validation was carried out using AutoDock software. Glioma gene expression and clinical data were obtained by TCGA and GTEx databases, and the core target genes were analyzed by bioinformatic analysis. RESULTS A total of 197 targets of Ginkgo biloba leaf and glioma were extracted, and hub genes were obtained. Molecular docking results showed that the target proteins of hub Genes of glioma involved STAT3, TNF, TP53, ACTB, VEGFA and GAPDH could bind efficiently to the related active components of Ginkgo biloba. Bioinformatic analysis indicated that the core target genes were significantly upregulated in glioma, and had potential diagnostic, prognostic and therapeutic value. CONCLUSIONS Ginkgo biloba leaf may play a role in the treatment of glioma by acting on core target proteins such as STAT3, TNF, TP53 and VEGFA through the main active components such as quercetin and luteolin, and play a role in the treatment of glioma by regulating oxidative stress, MEK/ERK, PI3K/AKT and other signaling pathways.