Related Experiment Video
Updated: May 17, 2026

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Berberine inhibits doxorubicin-triggered cardiomyocyte apoptosis via attenuating mitochondrial dysfunction and
Xiuxiu Lv1, Xiaohui Yu, Yiyang Wang
1Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
Abstract:
Cardiomyocyte apoptosis is an important event in doxorubicin (DOX)-induced cardiac injury. The aim of the present study was to investigate the protection of berberine (Ber) against DOX- triggered cardiomyocyte apoptosis in neonatal rat cardiomyocytes and rats. In neonatal rat cardiomyocytes, Ber attenuated DOX-induced cellular injury and apoptosis in a dose-dependent manner. However, Ber has no significant effect on viability of MCF-7 breast cancer cells treated with DOX. Ber reduced caspase-3 and caspase-9, but not caspase-8 activity in DOX-treated cardiomyocytes. Furthermore, Ber decreased adenosine monophosphate-activated protein kinase α (AMPKα) and p53 phosphorylation at 2 h, cytosolic cytochrome c and mitochondrial Bax levels and increased Bcl-2 level at 6 h in DOX-stimulated cardiomyocytes. Pretreatment with compound C, an AMPK inhibitor, also suppressed p53 phosphorylation and apoptosis in DOX-treated cardiomyocytes. DOX stimulation for 30 min led to a loss of mitochondrial membrane potential and a rise in the AMP/ATP ratio. Ber markedly reduced DOX-induced mitochondrial membrane potential loss and an increase in the AMP/ATP ratio at 1 h and 2 h post DOX exposure. In in vivo experiments, Ber significantly improved survival, increased stroke volume and attenuated myocardial injury in DOX-challenged rats. TUNEL and Western blot assays showed that Ber not only decreased myocardial apoptosis, caspase-3 activation, AMPKα and p53 phosphorylation, but also increased Bcl-2 expression in myocardium of rats exposed to DOX for 84 h. These findings indicate that Ber attenuates DOX-induced cardiomyocyte apoptosis via protecting mitochondria, inhibiting an increase in the AMP/ATP ratio and AMPKα phosphorylation as well as elevating Bcl-2 expression, which offer a novel mechanism responsible for protection of Ber against DOX-induced cardiomyopathy.
Insights
Berberine (Ber) protects against doxorubicin (DOX)-induced heart injury by reducing cardiomyocyte apoptosis. It preserves mitochondrial function and inhibits key signaling pathways, offering a novel therapeutic mechanism for doxorubicin-induced cardiomyopathy.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Doxorubicin (DOX) is a potent chemotherapy agent with known cardiotoxic side effects.
- Cardiomyocyte apoptosis is a primary mechanism underlying DOX-induced cardiac injury.
- Identifying protective agents against DOX cardiotoxicity is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the protective effects of berberine (Ber) against DOX-induced cardiomyocyte apoptosis.
- To elucidate the underlying molecular mechanisms of berberine's cardioprotective action.
Main Methods:
- In vitro studies using neonatal rat cardiomyocytes and MCF-7 breast cancer cells.
- In vivo studies involving doxorubicin-challenged rats.
- Assays included Western blot, TUNEL, caspase activity, mitochondrial membrane potential, and AMP/ATP ratio measurements.
Main Results:
- Berberine dose-dependently attenuated DOX-induced injury and apoptosis in cardiomyocytes, without affecting MCF-7 cell viability.
- Berberine inhibited caspase-3 and caspase-9 activity, reduced p53 and AMPKα phosphorylation, and modulated Bcl-2/Bax expression.
- Berberine preserved mitochondrial membrane potential, reduced the AMP/ATP ratio, improved survival, and attenuated myocardial injury in vivo.
Conclusions:
- Berberine demonstrates significant cardioprotective effects against doxorubicin-induced cardiotoxicity.
- Protection involves preserving mitochondrial integrity, inhibiting apoptosis signaling pathways, and modulating energy metabolism.
- Berberine represents a potential therapeutic strategy for preventing or treating doxorubicin-induced cardiomyopathy.
Related Concept Videos
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
The Intrinsic Apoptotic Pathway
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
Heart Failure Drugs: β-Blockers
Heart Failure Drugs: Inotropic Agents
Inhibition of Cdk Activity
