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.

Plos One
|October 19, 2012
PubMed

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.

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