Network toxicological analysis and mechanism prediction of cardiotoxicity of alkaloids in Aconiti Radix

doi:10.19803/j.1672-8629.2022.01.13

Abstract

Abstract: Objective To explore and predict cardiotoxic targets and mechanism of alkaloids in Aconiti Radix with network toxicology and molecular docking methods, and provide data for the safety of clinical application. Methods Literature related to toxicant alkaloids in Aconiti Radix was retrieved from TCMSP and CTD. SwissTargetPrediction online database was used to screen the target proteins of these ingredients while Cytoscape software was used to construct the toxicant alkaloids-target network. The target proteins of cardiotoxicity were predicted by CTD. The intersection of the two networks was considered to be the potential cardiotoxic targets of Aconiti Radix, which was analyzed to establish the protein-protein interaction (PPI) network by STRING database. The action mechanisms were predicted by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment with the help of Metascape database. The affinity and binding modes of the key proteins with toxic ingredients of Aconiti Radix were verified by AutoDock Vina software. Results There were 26 candidates for toxicant alkaloids, involving 33 target proteins of cardiotoxicity. The results of GO and KEGG enrichment analyses showed that the targets participated in the supply of blood to the heart and homeostasis of mall molecular substances by means of blood circulation and transmembrane transport. The influence of such targets as CHRM2, MAPK14, AGTR2 and PARP1 on many signaling pathways played an important role in the metabolism, development and form of the heart, and consequently cardiotoxicity occurred. Molecular docking results indicated that the majority of the toxicant alkaloids displayed good binding activities with the cardiotoxic targets, indicateing that hydrogen bonding, hydrophobic effect, and Pi-Pi bonding were the main forms of interactions. Conclusion Based on network pharmacology, it is proved that the interaction of alkaloids in Aconiti Radix with multiple protein targets and pathways results in cardiotoxicity, which can provide new clues to studies on cardiotoxic mechanisms of Aconiti Radix.

Key words: Aconiti Radix, network toxicology, molecular docking, alkaloid, aconitine, cardiotoxicity, mechanism prediction

CLC Number:

R288
R994.13

FENG Qun, YAO Jingchun, LI Xin, JING Fanbo, ZHANG Na, ZHANG Guimin. Network toxicological analysis and mechanism prediction of cardiotoxicity of alkaloids in Aconiti Radix[J]. Chinese Journal of Pharmacovigilance, 2022, 19(1): 62-68.

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