Cardiotoxicity of Aconiti Kusnezoffii Radix Based on Network Toxicology
10.13422/j.cnki.syfjx.20191425
- VernacularTitle: 基于网络毒理学探讨草乌心脏毒性
- Author:
Jun-xia HAO
1
;
Zi-sen GAO
1
;
Hao GAO
1
;
Kai-shun BI
1
;
Jian WANG
1
;
Zuo-jing LI
1
Author Information
1. School of Pharmacy, School of Pharmaceutical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China
- Publication Type:Research Article
- Keywords:
network toxicology;
Aconiti Kusnezoffii Radix;
cardiotoxicity;
path analysis;
molecular docking
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(19):161-169
- CountryChina
- Language:Chinese
-
Abstract:
Objective:The mechanism of action of cardiac toxicity of Radix Aconiti Agrestis was explored by establishing the active components-targets network of Radix Aconiti Agrestis, protein interaction network, the biological function and pathway network of targets, and using molecular docking technology. Methods:The Traditional Chinese Medicine Systems Pharmacology(TCMSP) database and the Comparative Toxicogenomics Database(CTD) were used to filtrate the toxic candidates of Radix Aconiti Agrestis. Predicting the functional targets of toxic candidates of Radix Aconiti Agrestis by PharmMapper and compared with the cardiac related gene proteins found in the human gene database (GeneCards), and the overlapping proteins were selected as potential cardiac toxicity targets of Radix Aconiti Agrestis. The Cytoscape software was used to construct the network between toxic candidate components and targets. The protein interaction network was mapped by the String database combined with Cytoscape software. The biological functions of the targets and the involved pathways were analyzed with the DAVID platform.The binding of the key proteins with certain toxic candidate components of Radix Aconiti Agrestis was verified by Discover Studio software finally. Results:There were six candidates for toxic ingredients, which involving 27 cardiac toxicity targets. Network analysis results show that the targets were mainly by participating in the heart of phosphorus metabolism, regulation and other related phosphorus metabolism and regulation of phosphorylation and FKBP1A,TGF4-β2, INSR targets to have an important impact on the metabolism,development and form of the heart,and further to have cardiac toxicity. Conclusion:Based on the characteristics of the multi-component, multi-target and multi-pathway of traditional Chinese medicine, the mechanism of cardiac toxicity of Radix Aconiti Agrestis was explored and its possible toxicity was predicted, which provided a new idea and method for further research on the mechanism of cardiac toxicity of Radix Aconiti Agrestis.
