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Potential Mechanisms of Trimetazidine and Coenzyme Q10 Against Antipsychotic-Induced Myocarditis: A Network
Ximing Chen1, Dongyin Zhuo2,3, Jiatong Zou1
1Laboratory of Computational Biology and Computational Psychiatry (CBCP-Lab), Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin Medical University, Tianjin, China.
Background:
Antipsychotic-induced myocarditis is a rare but potentially fatal adverse event associated with antipsychotic treatment. Trimetazidine (TMZ) and coenzyme Q10 (CoQ10) have shown potential cardioprotective effects. Thus, they may represent adjunctive therapeutic candidates for antipsychotic-induced myocarditis. However, the underlying molecular mechanisms and therapeutic relevance of this remain unclear. This study aimed to identify the potential pharmacological mechanisms and therapeutic targets of TMZ and CoQ10 in antipsychotic-induced myocarditis.
Methods:
Drug- and disease-associated targets were retrieved or predicted using SwissTargetPrediction, SEA, PharmMapper, Super-PRED, and GeneCards. Overlapping drug-disease targets were identified and used to construct a protein-protein interaction network and determine the core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed using DAVID. Finally, molecular docking and molecular dynamics simulations were conducted to evaluate ligand-target interactions and the stability of the selected complexes.
Results:
Twenty-six overlapping TMZ-disease targets and 27 overlapping CoQ10-disease targets were identified. GO and KEGG enrichment analyses revealed that these targets were involved in multiple biological processes, cellular components, molecular functions, and signaling pathways. Thirty-nine unique drug-disease intersection targets were obtained after merging the TMZ-disease and CoQ10-disease targets and five core targets were identified: STAT3, NFKB1, HIF1A, CASP3, and MMP9. Further GO and KEGG enrichment analyses were conducted for the 39 drug-disease intersection targets. GO enrichment analysis indicated that the apoptotic process was greatly enriched, whereas KEGG analysis highlighted the PI3K/AKT signaling pathway. Molecular docking suggested that TMZ and CoQ10 could form stable interactions with the core targets, supporting their potential therapeutic relevance. The molecular dynamics simulations further supported the stability of the selected ligand-target complexes.
Conclusions:
Network pharmacology, molecular docking, and molecular dynamics simulations were used to investigate the potential pharmacological mechanisms underlying the effects of TMZ and CoQ10 in antipsychotic-induced myocarditis. The findings provide theoretical and computational evidence for future experimental studies on TMZ and CoQ10 as potential adjunctive therapeutic candidates for antipsychotic-induced myocarditis.
