A network-based multi-target strategy to investigate cardioprotection effect against doxorubicin by quercetin / 中草药

ABSTRACT

Objective: To investigate the multi-target action mechanism of quercetin against doxorubicin-induced myocardial toxicity. Methods: Adult ICR mice were randomly divided into control group, doxorubicin group, and quercetin treatment group (n = 8). After experiments, serum was collected for measurement of creatine kinase and lactate dehydrogenase, and cardiac tissue cryopreservation was rapidly excised for proteomics studies. Finally, a network of differential proteins and known target proteins of quercetin was constructed to identify target proteins of quercetin against doxorubicin-induced myocardial toxicity. Results: Quercetin significantly reduced the concentration of doxorubicin-induced elevated serum creatine kinase and lactate dehydrogenase, suggesting that quercetin can alleviate doxorubicin-induced myocardial damage. Proteomic results indicated that quercetin protected doxorubicin-induced cardiotoxicity by regulating differential expression of 40 proteins. Gene ontology analysis and pathway enrichment analysis showed that quercetin mainly exerted myocardial protection by regulating redox, energy metabolism, fatty acid metabolism, high density lipoprotein, and apoptosis. Further network analysis screened out 11 proteins that quercetin targeted to regulate the above biological processes and pathways. Conclusion: Quercetin relieves doxorubicin-induced myocardial toxicity by targeting 11 proteins and then regulating redox, energy metabolism, fatty acid metabolism, high-density lipoprotein, and apoptosis.