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Updated: Dec 17, 2025
Author Spotlight: Novel Intraperitoneal Injection Method for Zebrafish Cardiotoxicity Models
Published on: March 29, 2024
Potential Molecular Mechanisms and Drugs for Aconitine-Induced Cardiotoxicity in Zebrafish through RNA Sequencing and
Mingzhu Wang1, Yanan Shi1, Lei Yao1
1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China (mainland).
Abstract:
BACKGROUND Accumulating evidence suggests that cardiotoxicity is one of the main manifestations of aconitine (AC) poisoning. However, the molecular mechanism of AC-induced cardiotoxicity remains unclear, there is little direct evidence for therapeutic targets and drugs of AC-induced cardiotoxicity. MATERIAL AND METHODS Zebrafish were exposed to AC to evaluate cardiotoxicity by calculating the heart rates and observing the changes of cardiac and vascular structure. RNA-seq (RNA sequencing) and bioinformatics analysis were used to obtain differentially expressed genes (DEGs). The anti-AC cardiotoxicity compound was identified via connectivity map (CMAP) analysis and molecular docking. RESULTS AC-induced cardiotoxicity in zebrafish predominantly included arrhythmias, extended sinus venous and bulbus arteriosus (SV-BA) distance, and larger pericardial edema aera. A total of 1380 DEGs were identified by RNA-seq and bioinformatics analysis. cyclin-dependent kinase-1 (CDK1) was screened as the hub gene and the most potential therapeutic target due to its significant downregulation in cardiotoxicity based on protein-protein interaction (PPI) and drug-gene interaction (DGIdb) network analysis. Cell cycle signal pathway was the most significant pathways identified in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Furthermore, the expression of CDK1 was validated in the Gene Expression Omnibus (GEO) database GSE71906, GSE65705, and GSE95140. Finally, heptaminol was identified as a novel anti-AC cardiotoxicity compound via CMAP analysis and molecular docking. CONCLUSIONS Totally, hub genes and key pathways identified in this study can aid in the understanding of the molecular changes in AC-induced cardiotoxicity. Meanwhile, we provide a systematic method to explore drug toxicity prevention and treatment.
Insights
Aconitine (AC) poisoning causes cardiotoxicity, impacting heart rate and structure. This study identifies cyclin-dependent kinase-1 (CDK1) as a key target and heptaminol as a potential therapeutic compound for AC-induced heart damage.
Area of Science:
- Toxicology
- Molecular Biology
- Pharmacology
Background:
- Aconitine (AC) poisoning is a significant cause of cardiotoxicity.
- The precise molecular mechanisms underlying AC-induced cardiotoxicity are not fully understood.
- There is a lack of identified therapeutic targets and drugs for AC cardiotoxicity.
Purpose of the Study:
- To elucidate the molecular mechanisms of AC-induced cardiotoxicity.
- To identify potential therapeutic targets and drugs for AC cardiotoxicity.
Main Methods:
- Zebrafish models were used to assess AC-induced cardiotoxicity.
- RNA sequencing (RNA-seq) and bioinformatics identified differentially expressed genes (DEGs).
- Connectivity Map (CMAP) analysis and molecular docking were employed to find potential therapeutic compounds.
Main Results:
- AC exposure in zebrafish resulted in arrhythmias, extended SV-BA distance, and pericardial edema.
- 1380 DEGs were identified, with cyclin-dependent kinase-1 (CDK1) highlighted as a crucial downregulated hub gene.
- The cell cycle pathway was identified as a significantly affected pathway.
- Heptaminol was identified as a novel compound with potential anti-AC cardiotoxicity effects.
Conclusions:
- The identified hub genes and pathways enhance understanding of AC-induced cardiotoxicity molecular changes.
- This study provides a systematic approach for exploring drug toxicity prevention and treatment strategies.
- CDK1 is a potential therapeutic target, and heptaminol shows promise for treating AC cardiotoxicity.
