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Updated: May 22, 2025
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Leonurine alleviates doxorubicin-induced myocarditis in mice via MAPK/ERK pathway inhibition
Dachao Tang1, Hu Jin1, Meise Lin1
1Department of Cardiovascular Medicine, Wenzhou Hospital of Traditional Chinese Medicine Wenzhou 325000, Zhejiang, China.
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.
Insights
Naturally derived leonurine (Leo) protects against doxorubicin (Dox)-induced myocarditis by reducing inflammation and apoptosis. Leo shows potential as a cardioprotective agent by inhibiting key inflammatory pathways.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Molecular Biology
Background:
- Doxorubicin (Dox) is a widely used chemotherapy agent with known cardiotoxicity.
- Myocarditis, or inflammation of the heart muscle, is a serious side effect of Dox treatment.
- Identifying protective agents against Dox-induced cardiotoxicity is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the cardioprotective effects of leonurine (Leo) against Dox-induced myocarditis.
- To elucidate the underlying mechanisms of Leo's protective action.
- To assess Leo's impact on inflammatory and apoptotic pathways in the heart.
Main Methods:
- A mouse model of Dox-induced myocarditis was established.
- Levels of inflammatory cytokines were measured using ELISA.
- Histopathological changes and apoptosis were assessed via HE and TUNEL staining.
- Protein expression was analyzed by Western blot.
- In vitro studies on H9c2 cells evaluated cell viability, inflammatory markers, and oxidative stress.
Main Results:
- Leo significantly reduced inflammatory cytokine levels in serum, cardiac tissue, and cell culture supernatants.
- Leo suppressed Dox-induced myocardial cell apoptosis by modulating the BCL2 signaling pathway.
- In vitro, Leo decreased inflammatory cytokines and oxidative stress markers in H9c2 cells.
- Leo treatment inhibited the activation of MAPK/ERK pathways.
Conclusions:
- Leonurine (Leo) demonstrates significant cardioprotective effects against doxorubicin (Dox)-induced myocarditis.
- These effects are mediated through anti-inflammatory mechanisms and the inhibition of apoptosis.
- Leo's ability to inhibit MAPK/ERK pathways suggests its therapeutic potential as a cardioprotective agent.
