基于网络药理学的山豆根神经毒性机制探讨  

Study on mechanism of nerve toxicity of Sophora tonkinensis Gagnep based on network pharmacology

作　　者：刘畅 俸婷婷 刘雄伟 石慧 沈奇涛 周英 LIU Chang;FENG Ting-ting;LIU Xiong-wei;SHI Hui;SHEN Qi-tao;ZHOU Ying(School of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Research Center for the Application and Development of Medicineand Food Dual-use Resources,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学药学院,贵州贵阳550025 [2]贵州中医药大学药食两用资源应用与开发研究中心,贵州贵阳550025

出　　处：《中国药理学通报》2020年第8期1165-1173,共9页Chinese Pharmacological Bulletin

基　　金：国家重点研发计划项目(No 2018YFC1708100);贵州省高层次创新型人才培养项目(No 2015-4032);贵州中医药大学2018年度学术新苗培养及创新探索专项(No 2018-5766-9);贵州中医药大学博士启动基金(No 2019-04)。

摘　　要：目的建立山豆根活性成分-靶点及相关的通路网络,探讨山豆根神经毒性的作用机制。方法利用TCMSP和CTD数据库筛选山豆根有毒化合物,通过Swiss Target Prediction平台预测靶点;与GeneCards数据库中神经毒性蛋白进行比对,筛选山豆根潜在的神经毒性靶点,构建山豆根毒性成分-靶点网络。确定山豆根神经毒性的特异性靶点,并进行信号通路富集分析。结果山豆根中筛选到15种有毒候选成分,涉及89个神经毒性作用靶点,其中ACHE、CHRNA3、CHRNA4、MAOA、PARP1、PTGS1、PTGS2等可能是山豆根神经毒性的关键靶点。KEGG通路分析表明,山豆根作用于神经系统相关的信号通路,如含血清素的神经突触、多巴胺能神经突触、胆碱能突触等,还对PI3K-Akt信号通路、MAPK信号通路、TNF信号通路和钙离子信号通路等进行调控。结论研究初步揭示山豆根神经毒性作用的关键靶点及涉及的信号通路,为进一步研究其神经毒性作用机制研究提供参考和依据。Aim To explore the mechanism of nerve toxicity of Sophora tonkinensis Gagnep.and its active component-target,a network of its biological function and related pathway with the target were established.Methods The toxic components of the Sophora tonkinensis Gagnep.was obtained from the TCMSP and CTD database.Target prediction was carried out on SwissTargetPrediction platform.The nerve toxicity related targets were screened by GeneCards databases and overlapping proteins were obtained as potential nerve toxicity targets of Sophora tonkinensis Gagnep.Meanwhile,the candidate components-target network of Sophora tonkinensis Gagnep.was established by Cytoscape software combined with String database.Furthermore,the gene information was obtained from the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,and then the target pathway network model was established.Results In this study,15 toxic components and 89 effective targets were predicted.The gene,such as ACHE,CHRNA3,CHRNA4,MAOA,PARP1,PTGS1 and PTGS2 might be the key targets of nerve toxicity of Sophora tonkinensis Gagnep.KEGG pathway analysis showed that Sophora tonkinensis Gagnep.was directly engaged in the signaling pathways in nervous system,such as Serotonergic synapse,Dopaminergic synapse,Cholinergic synapse,Sophora tonkinensis Gagnep.regulated other signaling pathways,such as PI3K-Akt signaling pathway,MAPK signaling pathway,TNF signaling pathway,calcium signaling pathway and others.Conclusion The preliminary discovery of key targets and signaling pathways lays basis for further research on nerve toxicity mechanism of Sophora tonkinensis Gagnep.

关 键 词：山豆根 神经毒性 网络药理学 靶点 胆碱能突触 钙信号通路 

分 类 号：R282.71[医药卫生—中药学] R284.1[医药卫生—中医学]