Leonurine alleviates doxorubicin-induced myocarditis in mice via MAPK/ERK pathway inhibition.

OBJECTIVE

To investigate the effects of naturally derived leonurine (Leo) on doxorubicin (Dox)-induced myocarditis and analyze its potential mechanisms.

METHODS

Dox was intraperitoneally injected to establish a myocardial injury model in mice. The effect of Leo on inflammatory cytokine levels in myocardial tissue was assessed by ELISA. Pathological changes in myocardial tissue and apoptosis in myocardial cells were observed using hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Protein levels were analyzed by Western blot (WB). Mouse myocardial H9c2 cells were divided into control group, Dox group, Leo (10 μmol/L) + Dox group, and Leo (20 μmol/L) + Dox group. Cell viability was assessed using Cell Counting Kit-8 (CCK8), and the levels of inflammatory cytokines were measured. The oxidation level and protein levels in H9c2 cells were also detected.

RESULTS

Leo significantly reduced the levels of inflammatory cytokines in both serum and cell culture supernatant. Additionally, Leo also decreased the levels of inflammatory cytokines in cardiac tissue. Moreover, Leo suppressed Dox-induced myocardial cell apoptosis by modulating the BCL2 signaling pathway. In vitro studies revealed that both inflammatory cytokines and oxidative stress markers were decreased after treatment with Leo.

CONCLUSION

Leo exerts significant cardioprotective effects through anti-inflammatory mechanisms, likely mitigating Dox-induced myocardial inflammation by inhibiting the activation of MAPK/ERK pathways. These findings highlight Leo's potential as a promising cardioprotective agent, underscoring its therapeutic promise.