基于网络分析的大黄毒性作用机制

Study on the mechanism of action of toxicity of Radix et Rhizoma Rhei based on network analysis

目的采用网络毒理学的方法预测并分析大黄中有毒物质的相关毒性作用机制。方法将在中药系统药理数据库和分析平台(TCMSP)可以查询到已知的大黄的化合物成分,与在比较毒物基因组学数据库(CTD)中查询到的大黄化合物成分的毒物信息进行比对,筛选出大黄中9种有毒成分,并用Swiss Target Prediction服务器等查询有毒成分的靶点信息,进而使用Cytoscape软件构建了毒性成分-靶点互作网络以及靶点之间的互作网络,发现了其中Degree值最高的几种靶点蛋白。使用DAVID生物信息平台,进行基因本体(GO)分析以及京都基因和基因组百科全书(KEGG)通路富集分析,得出了大黄中有毒物质可能通过哪些通路对人体产生危害。结果大黄中毒性成分可能通过p53信号通路、钙离子信号通路、Toll样受体信号通路、Wnt信号通路引起毒性;还可能通过细胞凋亡调节引起毒性及其他自身免疫系统疾病。结论初步探究了大黄的毒理机制,并预测了大黄可能存在的毒性,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 toxic mechanism of Radix et Rhizoma Rhei by using network toxicology.Methods Comparing the chemical composition of the Radix et Rhizoma Rhei obtained from the TCMSP database and the toxicological information obtained from the CTD database,we screened out nine toxic components from Radix et Rhizoma Rhei,using the Swiss Target Prediction website to find detailed information of the target proteins of the nine components.Furthermore,Cytoscape software was used to construct the toxic component-target interaction network and the interaction network between targets and several target proteins with the highest degree of association were found.The DAVID bioinformation platform was used to carry out gene ontology(GO)analysis and Kyoto gene and genome encyclopedia(KEGG)pathway enrichment analysis,and the possible harm of toxic substances in Radix et Rhizoma Rhei to human body through which pathways were obtained.Results The toxic substances in Radix et Rhizoma Rhei may induce toxicity through Toll-like receptor signaling pathway,MAPK signaling pathway,Nod-like receptor signaling pathway,RIG-I like receptor signaling pathway,mTOR signal pathway.Radix et Rhizoma Rhei is also possible to cause toxicity and other autoimmune diseases by apoptosis regulation.Conclusion The toxicological mechanism of Radix et Rhizoma Rhei was preliminarily explored,and the possible toxicity of Radix et Rhizoma Rhei was predicted,which provided a new idea for the prediction of the toxicity of traditional Chinese medicine components and the exploration of the toxicity mechanism.