基于网络药理学和分子对接的蛇枝黄苓汤治疗脑肿瘤的分子机制研究

Study on the molecular mechanism of Shezhihuangling decoction in the treatment of brain tumor based on network pharmacology and molecular docking

目的应用网络药理学和分子对接的方法,探讨蛇枝黄苓汤(SZHL)治疗脑肿瘤的分子机制和靶点。方法通过TCMSP平台搜索SZHL的活性成分,根据其透过血脑屏障的能力,将其分为中枢成分和外周成分;通过GEO数据库挖掘脑肿瘤的差异基因,使用Cytoscape 3.8.0软件可视化成分-靶标网络;通过String平台构建治疗靶标的蛋白互作网络,使用Bioconductor进行GO和KEGG富集分析,使用Cytoscape进行核心靶点-KEGG网络的构建;使用Pymol、autodock、vina软件对关键靶点和药效成分进行分子对接。结果中枢成分-BT靶点网络由30个节点和58个边组成,外周成分-BT靶点网络包括68个节点和174个边;中枢通路主要涉及逆行大麻素受体信号通路、cAMP信号通路等,外周通路主要涉及TNF信号通路、IL-17信号通路、NF-kB信号通路等;中枢成分中的植物甾醇、常春藤皂苷元与PTGS2、CHRM1、CHRM3、NR3C2、CASP8等靶点有较强的结合活性,周围成分中槲皮素、山奈酚、木犀草素等与PTGS2、GABRA1、RELA、CCND1等靶点有强烈的对接能力。结论SZHL中的植物甾醇、常春藤皂苷元等成分具有透过血脑屏障的能力,发挥影响胆碱能细胞信号转导、诱导细胞凋亡等作用;槲皮素、山奈酚、木犀草素等周围成分,通过抗炎、调节免疫等机制发挥抗脑肿瘤的作用。

Objective To explore the molecular mechanism and target spot of Shezhihuangling(SZHL)decoction in the treatment of brain tumor based on network pharmacology and molecular docking.Methods Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)was used to search the active ingredients of SZHL.According to their ability of passing through the blood brain barrier,the ingredients were divided into the central nerve system(CNS)and peripheral nerve system(PNS).The differential genes were obtained from the GEO database.The Cytoscape 3.8.0 software was used to visualize target network and protein-protein interaction networks were constructed by String database.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)enrichment was conducted by Bioconductor software.Cytoscape was used to construct the key target genes of KEGG network.Pymol,Autodock and Vina software were applied to acquire the molecular docking results of key targets and pharmacodynamic components.Results The CNS components-BT targets network was consist of 30 nodes and 58 edges.The PNS-BT targets network was constructed with 68 nodes and 174 edges.The CNS signaling pathways included retrograde cannabinoid receptor signaling pathway,cAMP signaling pathway and so on.The PNS signaling pathways included TNF signaling pathway,IL-17 signaling pathway,and NF-κB signaling pathway.CNS component of phytosterols and hederogenin had strong binding activities with PTGS2,CHRM1,CHRM3,NR3C2 and CASP8.The PNS component of quercetin,kaempferol,and luteolin had strong binding activities with PTGS2,GABRA1,RELA and CCND1.Conclusion The phytosterols and hederagenin in SZHL Decoction have the ability to penetrate the blood-brain barrier,might influence cholinergic cell signal transduction and induce cell apoptosis.The peripheral ingredients of quercetin,kaempferol and luteolin have anti-brain tumor effect through anti-inflammatory and immune regulation mechanisms.