Key result
Tongmai Yangxin pills may reduce doxorubicin-induced cardiotoxicity by improving energy metabolism and inhibiting apoptosis.
Why the study?
Doxorubicin has high cardiotoxicity despite its anticancer activity, and the mechanism by which Tongmai Yangxin pills ameliorate this cardiotoxicity is unclear.
Tongmai Yangxin pills may protect against doxorubicin-induced cardiotoxicity by modulating energy metabolism and inhibiting myocardial apoptosis pathways.
Preclinical data support further mechanistic and translational studies; should not yet inform clinical use of Tongmai Yangxin pills.
Doxorubicin (DOX) is a broad-spectrum chemotherapeutic drug used in clinical treatment of malignant tumors. It has a high anticancer activity but also high cardiotoxicity. The aim of this study was to explore the mechanism of Tongmai Yangxin pills (TMYXPs) in ameliorating DOX-induced cardiotoxicity through integrated metabolomics and network pharmacology. In this study, first, an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) metabonomics strategy was established to obtain metabolite information and potential biomarkers were determined after data processing. Second, network pharmacological analysis was used to evaluate the active components, drug-disease targets, and key pathways of TMYXPs to alleviate DOX-induced cardiotoxicity. Targets from the network pharmacology analysis and metabolites from plasma metabolomics were jointly analyzed to select crucial metabolic pathways. Finally, the related proteins were verified by integrating the above results and the possible mechanism of TMYXPs to alleviate DOX-induced cardiotoxicity was studied. After metabolomics data processing, 17 different metabolites were screened, and it was found that TMYXPs played a role in myocardial protection mainly by affecting the tricarboxylic acid (TCA) cycle of myocardial cells. A total of 71 targets and 20 related pathways were screened out with network pharmacological analysis. Based on the combined analysis of 71 targets and different metabolites, TMYXPs probably played a role in myocardial protection through regulating upstream proteins of the insulin signaling pathway, MAPK signaling pathway, and p53 signaling pathway, as well as the regulation of metabolites related to energy metabolism. They then further affected the downstream Bax/Bcl-2-Cyt c-caspase-9 axis, inhibiting the myocardial cell apoptosis signaling pathway. The results of this study may contribute to the clinical application of TMYXPs in DOX-induced cardiotoxicity.
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Shu et al. (2023) studied Doxorubicin-induced cardiotoxicity. Tongmai Yangxin pills (TMYXPs) was evaluated on Metabolites and pharmacological targets. Tongmai Yangxin pills may ameliorate doxorubicin-induced cardiotoxicity by regulating energy metabolism and inhibiting myocardial cell apoptosis via the Bax/Bcl-2-Cyt c-caspase-9 axis.
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