基于网络药理学和分子对接技术探讨鹰嘴豆芽素A治疗神经胶质瘤的作用机制

目的 通过网络药理学、分子对接的方法探究鹰嘴豆芽素A治疗神经胶质瘤的作用机制。方法 检索中药系统药理学数据库与分析平台（traditional Chinese medicine systems pharmacology database and analysis platform，TCMSP）、TargetNet、Swiss Target Prediction等数据库和分析平台，筛选出鹰嘴豆芽素A对应靶点，利用DisGeNET、GeneCards等数据库获得神经胶质瘤的作用靶点。取药物与疾病的交集靶点，借助STRING数据库进行蛋白-蛋白相互作用(protein-protein interaction，PPI)分析，利用Cytoscape 3.9.1软件构建潜在靶点网络关系图。对交集靶点通过DAVID数据库进行本体论富集分析（gene ontology，GO）和京都基因和基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。通过DockThor数据库对鹰嘴豆芽素A和关键靶点进行分子对接，Pymol软件进行可视化处理。结果 共筛选出鹰嘴豆芽素A靶点149个，神经胶质瘤相关靶点5654个，药物与疾病交集靶点97个，核心靶点为表皮生长因子受体（epidermal growth factor receptor，EGFR）、雌激素受体（estrogen receptor，ESR1）、热休克蛋白（heat shock protein，HSP）90AA1、基质金属蛋白酶（matrix metalloproteinase，MMP）9、PPARG、PTGS2，靶点参与的功能主要与肿瘤细胞增殖、侵袭、凋亡等过程有关。GO富集分析发现鹰嘴豆芽素A在生物过程、细胞组成、分子功能多方面参与神经胶质瘤的治疗。KEGG通路108条，包括肿瘤、化学致癌作用-受体活性、脂质和动脉粥样硬化、PI3K/Akt等信号通路。分子对接结果显示鹰嘴豆芽素A与关键靶点均有较好的结合活性。结论 鹰嘴豆芽素A可能通过抑制肿瘤细胞增殖、诱导凋亡、增强化疗敏感性等发挥治疗神经胶质瘤的作用。

Mechanism of Biochanin A in treating gliomas based on network pharmacology and molecular docking

Objective To analyze the mechanism of Biochanin A in the treatment of Gliomas based on network pharmacology and molecular docking. Methods Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), TargetNet, Swiss Target Prediction were used to search the active components and targets of Biochanin A. DisGeNET, GeneCards databases were used to search the corresponding targets of Gliomas. The intersection of active components of Biochanin A and gliomas target were selected to obtain the potential target of Biochanin A in treating Gliomas. Protein gene interaction data were obtained by STRING database, and protein-protein interaction network was constructed by importing into Cytoscape software. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of the same target proteins of drug and disease were carried out by DAVID database. Molecular docking was performed by using DockThor and Pymol software. Results A total of 149 targets of Biochanin A, 5654 gliomas relate-genes, 97 common targets of Biochanin A and gliomas are collected. The key targets were epidermal growth factor receptor (EGFR), estrogen receptor (ESR1), heat shock protein (HSP)90AA1, matrix metalloproteinase (MMP)9, PPARG and PTGS2. The targets were mainly play an essential role in cell proliferation, invasion, cell apoptosis, and other biological pathways. GO enrichment analysis demonstrated that Biochanin A could involve the treatment of Gliomas in biological process, cell composition and molecular function. KEGG 108 signaling pathways mainly related to pathways in cancer, chemical carcinogenesis-receptor activation, Lipid and atherosclerosis, PI3K/Akt pathway. Molecular docking indicated that Biochanin A had a good bonding activity with the key targets. Conclusion Biochanin A may play a role in the treatment of glioma by inhibiting tumor cell proliferation, inducing apoptosis and enhancing chemotherapy sensitivity. The study built a foundation for drug development and innovative research.