Objective To explore the potential mechanisms of cardiotoxicity of Euodia rutaecarpa,a long-used traditional Chinese medicine,in order to contribute to clinical safety and risk prevention.Methods Network pharmacology was employed to analyze the target pathways of Euodia rutaecarpa that acted on the heart.In combination with untargeted metabolomics,the impact of Euodia rutaecarpa on cardiac metabolic pathways was investigated in order to find out about the potential mechanisms of cardiotoxicity.Results Network pharmacology identified 51 intersecting targets between Euodia rutaecarpa and cardiotoxicity,such as TNF,IL-6,IL-1β,TP53,and CASP3.These targets were involved in key signaling pathways such as the Advanced Glycation End Products-Receptor(AGE-RAGE)and Mitogen-Activated Protein Kinase(MAPK)pathways.Metabolomics analysis revealed metabolic pathways,including purine metabolism,biosynthesis of valine,leucine,and isoleucine,and the citric acid(TCA)cycle.The combination of network pharmacology and untargeted metabolomics suggested that the cardiotoxicity of Euodia rutaecarpa was related to myocardial energy metabolism,potentially via the disruption of the intracellular TCA cycle,purine metabolism,and protein synthesis and degradation.Conclusion The cardiotoxicity of Euodia rutaecarpa is closely related to its impact on myocardial energy metabolism and exhibits bidirectional effects on the heart.Clinicians should be cautious regarding dosage and symptoms while attaching importance to drug monitoring.
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