基于网络药理学和分子对接技术研究β-细辛醚治疗胶质母细胞瘤的作用机制

Mechanism ofβ-Asarone on the Treatment of Glioblastoma Multiforme Based on Network Pharmacology and Molecular Docking Techniques

目的:基于网络药理学和分子对接技术分析β-细辛醚(β-asarone)治疗多形性胶质母细胞瘤(GBM)的作用机制。方法:利用Pubchem和PharmMapper数据库检索β-asarone的作用靶点,通过Genecards,Disgenet和OMMI数据库检索GBM的疾病相关靶点。构建β-asarone和GBM共有靶点,将共有靶点导入STRING数据库进行蛋白互作网络分析,并进行GO功能和KEGG通路富集分析。应用Autodock软件进行成分-靶点分子对接。结果:共得到β-asarone和GBM共同靶点38个,AKT1、CASP3、HRAS、CDK2、MAP2K1等是关键核心靶点。富集分析发现共有靶点涉及蛋白质丝氨酸/苏氨酸激酶活性的正性调节、氧化应激反应、细胞周期蛋白依赖性蛋白激酶复合物、转移和增殖等信号通路。分子对接结果显示,β-asarone与五个核心靶蛋白均具有较好亲和力。结论:β-asarone可能通过多靶点、多通路协同发挥抗GBM作用。

Objective:To explore the molecular mechanism ofβ-asarone in glioblastoma multiforme(GBM)treatment based on the network pharmacology and molecular docking technology.Methods:The targets ofβ-asarone were obtained from Pubchem and PharmMapper database.Genecards,Disgenet and OMMI database were used to collect the targets of GBM.The obtained drug-disease targets were imported to STRING database for protein-protein interaction network.Moreover,GO function and KEGG pathway enrichment analysis were carried out.Finally,with the aid of Autodock tools,the key active ingredients and core targets were docked by molecular docking.Results:After intersection,a total of 38 core targets were selected fromβ-asarone and GBM,of which AKT1,CASP3,HRAS,CDK2 and MAP2 K1 were the core targets of this study.Enrichment analysis showed that the common targets were mainly involved in protein serine/threonine kinase activity of positive regulation,oxidative stress response,cyclin-dependent protein kinase complex,metastasis and proliferation of signaling pathway.Through Autodock software,β-asarone has well affinity with five core targets proteins.Conclusion:β-asarone may exert anti-GBM effect through multi-targets and multi-pathway.