银杏叶治疗胶质母细胞瘤机制研究  

Research on the Mechanism of Ginkgo Folium to Treat Glioblastoma

作　　者：杨甫 王刘丽 李金星[2] 孙爱刚[2] 伏瑶 王增勇 王明光[2] Yang Fu;Wang Liuli;Li Jinxing;Sun Aigang;Fu Yao;Wang Zengyong;Wang Mingguang(Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Department of Neurosurgery,Linyi People's Hospital,Linyin 371300,China;Lanshan Matermal and Child Health Hospital,Linyi 276003,China;Central Laboratory,Linyi People's Hospital,Linyin 371300,China)

机构地区：[1]广州中医药大学,广东广州510006 [2]山东省临沂市人民医院神经外科,山东临沂371300 [3]兰山区妇幼保健院,山东临沂276003 [4]临沂市人民医院中心实验室,山东临沂371300

出　　处：《南开大学学报（自然科学版）》2023年第1期26-34,共9页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：Supported by the Doctoral Innovation Project of Linyi People’s Hospital(2018LYBS12)。

摘　　要：胶质母细胞瘤(GBM)是人类中枢神经系统肿瘤中发病率高、侵袭性强的恶性肿瘤.胶质母细胞瘤发生和发展的原因尚不清楚.银杏叶(GF)提取物可以减少裸鼠U-87胶质瘤细胞系的生长,然而,作用机制不清楚.在本研究中,网络药理学、分子对接和细胞实验被用来阐释银杏叶治疗胶质母细胞瘤的潜在的分子作用机制.从TCMSP数据库中获得银杏叶的有效成分和作用靶点,STRING数据库用于蛋白质相互作用分析,Cytoscape软件构建“成分-靶点”网络和PPI网络.R语言分析用来GO富集分析和KEGG通路分析.另外,Auto Dock Vina软件进行活性成分与核心靶点的分子对接验证.最后,通过细胞实验验证GF中的有效化合物对胶质母细胞瘤的抑制作用.结果表明,银杏叶有27个潜在有效成分和112个潜在靶点.从6个数据库中筛选出7 435个胶质母细胞瘤作用靶点.银杏叶与胶质母细胞瘤交集靶点98个.银杏叶共有18种核心有效成分,如槲皮素、山柰酚、木犀草素等以及10个相对应核心靶点ESR1、RELA、FOS、CCD1、EGFR、AR、HIF1A、MAPK8、NCOA1和MDM2.富集分析结果表明,银杏叶治疗胶质母细胞瘤主要参与生物过程,如细胞对化学应激的反应、对氧化应激的响应和转录调节复合物等.KEGG信号通路主要富集在PI3K-Akt、MAPK和TNF信号通路等.分子对接的结果验证了银杏叶的有效成分槲皮素(QUE),木犀草素(QUE)和山奈酚(KAE)与10个相对应的核心靶点具有良好结合活性.体外细胞实验表明,槲皮素、木犀草素和山柰酚抑制了人胶质母细胞瘤U251细胞活力.可以得出结论,银杏叶通过多组分、多靶点和多通路治疗胶质母细胞瘤,为银杏叶治疗胶质母细胞瘤的临床应用提供了理论基础.Glioblastoma(GBM) is a malignant tumor with a high incidence rate and high invasion in human central nervous system tumors. However, the causes of the occurrence and development of glioblastoma are not clear. Although Ginkgo Folium(GF) extract can reduce the growth of U-87 glioma cell lines in nude mice, the action mechanism remains unclear. In this study, network pharmacology, molecular docking, and cell experiment were utilized to explore the underlying molecular mechanism of GF in treating GBM. The effective ingredients and action targets of GF were obtained from the TCMSP database.STRING database was applied for protein interaction analysis and Cytoscape software was used to build the "compound-target-disease" network and PPI network. The R language was adopted as gene ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Auto Dock software was used for molecular docking verification. A cell experiment was employed to verify the inhibition of GBM by the effective compounds in GF. The results showed that 27 potential effective components and112 potential targets of GF were selected. 7 435 targets of GBM were screened from six databases, and98 overlapping targets were obtained. In active component-target network, quercetin, kaempferol, stigmasterol, and luteolin were the important active components. In PPI network, ESR1, RELA, FOS,CCD1,EGFR, AR, HIF1A, MAPK8, NCOA1, and MDM2 were the core targets. GO and KEGG analyses showed that the main pathways of GF in treating GBM involved PI3K-Akt, MAPK, and TNF signaling pathway. The results of molecular docking verified the good binding activity of the key pharmacodynamic molecules with the core targets. Cell experiments showed that quercetin(QUE), luteolin(LUT), and kaempferol(KAE) can inhibit cell viability in GBM cell lines U251. It can be concluded GF is the result of multi-component, multi-target, and multi-pathway interaction in the treatment of GBM, which provided a theoretical basis for the clinical application of GF in the tr

关 键 词：胶质母细胞瘤 银杏叶 机制 网络药理学 分子对接 

分 类 号：O177[理学—数学]