基于网络药理学探讨鸡血藤对糖尿病周围神经病变的作用机制

Investigating the action mechanism of Jixueteng on diabetic peripheral neurpthy based on network pharmacology

目的:应用网络药理学研究鸡血藤治疗糖尿病周围神经病变(Diabetic Peripheral Neuropathy,DPN)的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)检索鸡血藤的主要有效成分及作用靶点,应用GeneCards数据库检索DPN的关键靶点,接着使用R语言绘制韦恩图得到鸡血藤治疗DPN的共同靶点;使用Cytoscape 3.7.1软件绘制"鸡血藤-成分-DPN-靶点"的调控网络并在String平台构建蛋白质相互作用网络,最后使用Bioconductor和R语言进行基因本体论(GO)富集分析和京都基因和基因组数据库(KEGG)通路富集分析。结果:鸡血藤可能通过木犀草素、刺芒柄花素、甘草查尔酮a、驴食草酚、β-谷甾醇、毛蕊异黄酮等活性成分作用于环氧合酶2(Cyclooxygenase-2)、类固醇激素受体(Androgen Receptor,AR)、肾上腺素能β2受体(Adrenergic,beta-2,ADRB2)、糖原合成酶激酶-3(Glycogen Synthase Kinase 3 beta,GSK3B)、丝裂原活化蛋白激酶14(Mitogen-Activated Protein Kinase 14,MAPK14)等关键靶点,参与AGE-RAGE信号通路、癌症中的蛋白多糖人巨细胞病毒感染、磷脂酰肌醇3激酶(Phosphatidylinositol 3-Kinase,PI3K)-蛋白激酶B(Akt)信号通路、卡波西肉瘤相关疱疹病毒感染、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路、白细胞介素(Interleukin,IL)-17信号通路等生物过程,从而治疗DPN。结论:鸡血藤可能通过参与AGE-RAGE信号通路等相关生物功能及通路作用于PTGS2、AR等疾病靶点治疗DPN,显示了鸡血藤多成分、多靶点、多通路治疗DPN的作用机制。

Objective:To study the action mechanism of Jixueteng(Millettia reticulata)on DPN.Methods:The main effective components and action targets of Jixueteng were retrieved in TCMSP database.The key targets for the DPN were retrieved in GeneCards database.Then the Venn diagram was drew by R language software to get the common targets of treating DPN with Jixueteng.The control network of Jixueteng-components-DPN-targets was drew by Cytoscape 3.7.1 software.The PPI network was constructed on the String platform.Finally,GO enrichment analysis and KEGG pathway enrichment analysis were performed by bioconductor and R language softwares.Results:Jixueteng may act on key targets such as PTGS2,AR,ADRB2,GSK3B,MAPK14 and so on through active ingredients such as luteolin,formononetin,licorice Chalcone A,Donkey herbivorous phenol,β-sitosterol,mullins isoflavones,etc.,and take part in regulating biological processes such as AGE-RAGE signaling pathway,proteoglycan human cytomegalovirus infection in cancer,PI3K-Akt signaling pathway,Kaposi’s sarcoma-related herpes virus infection,MAPK signaling pathway,IL-17 signaling pathway then to treat VPN.Conclusion:The effects of Jixueteng on DPN can be reflected by the drug-ingredient-target-disease network,shows multi-component,multitarget and multi-pathway action mechanism of Chinese materia medica,and provides basis and ideas for the follow-up research on DPN.