基于网络分析的鱼腥草毒性作用机制

Study on the mechanism of action of the toxicology of Houttuynia cordata based on network analysis

目的采用网络毒理学的方法预测并分析鱼腥草中主要活性物质的相关毒性作用机制。方法通过中药系统药理数据库和分析平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)比较毒物基因组学数据库(the comparative toxicogenomics database,CTD)筛选出鱼腥草中6种有毒活性成分,并用Swiss Target Prediction服务器预测有毒活性成分的靶点信息,进而使用Cytoscape软件构建了有毒活性成分-靶点互作网络以及靶点之间的互作网络。使用DAVID(the database for annotation,visualization and integrated discovery)数据库,进行基因本体分析以及京都基因和基因组百科全书通路富集分析,得出了鱼腥草中有毒物质可能通过哪些通路对人体产生危害。结果研究结果显示,鱼腥草有毒活性成分对应的联系度最高的蛋白PTGS2、PRSS1、MAPT、SLC6A2等以及有毒活性成分可能通过Toll样受体信号通路、MAPK信号通路、Nod样受体信号通路、RIG-I样受体信号通路、mTOR信号通路引起过敏反应;可能抑制中枢神经系统;还可能通过对细胞凋亡的调节引起其他自身免疫系统疾病。结论初步探究了鱼腥草的毒理机制,并预测了鱼腥草可能存在的毒性,并为预测中药成分的毒性以及探究毒性机制提供了新思路。

Objective To predict and analyze the related toxicity mechanism of the main active substances in Houttuynia cordata by means of network toxicology.Methods Six toxic active ingredients of Houttuynia cordata were screened through the Comparative Toxicology Genomics Database(CTD)and Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),and Swiss Target Prediction server was used to predict toxicity.Target information of active ingredients was then used to construct target interaction network of toxic active ingredients and interaction network between targets by Cytoscape software.Gene ontology analysis and pathway enrichment in Kyoto Encyclopedia of Genes and Genomes were performed using the DAVID(the database for annotation visualization integrated discovery)database.It was concluded that how the toxic substances in Houttuynia cordata may cause harm to human body.Results It showed that PTGS2,PRSS1,MAPT,SLC6 A2 and other proteins with the highest degree of association with the toxic active ingredients of Houttuynia cordata and the toxic active ingredients may pass through Toll-like receptor signaling pathway,MAPK signaling pathway,Nod-like receptor signaling pathway,RIG-I receptor signaling pathway and mTOR signaling pathway that could induce allergic reaction.Besides,it may inhibit the central nervous system and cause other autoimmune system diseases by regulating apoptosis.Conclusion The toxicological mechanism of Houttuynia cordata was preliminarily explored and the possible toxicity of Houttuynia cordata was predicted.Therefore,it provided a new way to predict the toxicity of traditional Chinese medicine and explore the toxic mechanism.