基于网络分析细辛毒理学

Toxicology of Asari Radix et Rhizoma Based on Network Analysis

目的:采用网络毒理学的方法,通过建立化合物、蛋白、基因和毒物反应的网络关系,分析细辛中有毒物质的毒理作用机制,预测未知毒性。方法:通过在中药系统药理数据库和分析平台(TCMSP)数据库查询到的细辛候选化合物,以及在比较毒物基因组学数据库(CTD)中查询到的毒物信息的比对,筛选出细辛中13种有毒成分,并用Pharm Mapper Server中查询到13种成分相应的靶点蛋白等详细信息。使用Cytospace软件对这13种化学成分以及对应靶点蛋白,构建了网络结构图,发现了其中联系度最高的几种靶点蛋白。使用Cytospace软件中的Clue GO+Clue Pedia插件,进行gene ontology(GO)基因本体分析以及京都基因和基因组百科全书(KEGG)通路富集分析,得出了细辛中有毒物质可能通过哪些通路对人体有害。结果:细辛中毒性成分可能通过p53,白细胞介素(IL)-17,核转录因子(NF)-kappa B,肿瘤坏死因子(TNF)-α信号通路,细胞凋亡通路诱导肿瘤以及癌的形成;通过对神经元的调节,对中枢神经系统产生抑制作用;还可能通过IL-17,TNF-α和细胞凋亡调节引起其他自身免疫系统疾病。结论:探讨细辛的毒理机制,并预测了细辛可能存在的毒性,并为预测中药成分的毒性以及探究毒性机制提供了一个方法。

Objective:To analyze the known mechanism of toxicology and predict the unknown toxicity in Asari Radix et Rhizoma sinensis by establishing the network relationship of compound,protein,gene and toxicant reaction.Method:After comparing the Asari Radix et Rhizoma candidate compounds obtained from the traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database and the toxicological information obtained from the Comparative Toxicogenomics Database(CTD)database,we screened out 13 toxic components from Asari Radix et Rhizoma.And use the Pharm Mapper Server website to find the detailed information of target proteins of the 13 components.The network structure of these 13 chemical components and their corresponding target proteins were drawn by using Cytospace software,and several target proteins with the highest degree of association were found.ClueGO+CluePedia plug-in of Cytospace software was applied in gene ontology(GO)enrichment analysis of genes and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis,so as to determine the pathways through which toxic substances in Asari Radix et Rhizoma might be harmful to human body.Result:The toxic substances in Asari Radix et Rhizoma may induce tumor and cancer formation through p53 signaling pathway,interleukin(IL)-17 signaling pathway,nuclear factor(NF)-kappa B signaling pathway,tumor necrosis factor(TNF)-signaling pathway.Asari Radix et Rhizoma could inhibit the central nervous system by regulating apoptosis pathways and neurons,and may also cause other autoimmune diseases by IL-17,TNF-αpathway and apoptosis regulation.Conclusion:This study preliminarily explores related mechanisms of toxicity of Asari Radix et Rhizoma,this method can be used to predict toxicity and explain toxicity mechanism of traditional Chinese medicine.