Punicalagin Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via Activation of AMPK

Am J Chin Med. 2017;45(1):53-66. doi: 10.1142/S0192415X17500057. Epub 2017 Jan 13.

Abstract

Punicalagin (PUN), a major bioactive component in pomegranate juice, has been proven to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) insult via anti-oxidant properties. This study aims to investigate whether PUN provides cardioprotection against myocardial I/R (MI/R) injury and the underlying mechanisms. PUN (30[Formula: see text]mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for one week before the operation. MI/R was induced by ligating the left anterior descending coronary artery for 30[Formula: see text]min and subsequent reperfusion for 3[Formula: see text]h. PUN pretreatment conferred cardioprotective effects against MI/R injury by improving cardiac function, limiting infarct size, reducing serum creatine kinase-MB and lactate dehydrogenase activities, and suppressing cardiomyocyte apoptosis. Moreover, PUN pretreatment inhibited I/R-induced myocardial oxidative stress as evidenced by decreased generation of superoxide content and malonaldialdehyde formation and increased antioxidant capability. Furthermore, PUN pretreatment increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in I/R hearts. AMPK inhibitor compound c inhibited PUN-enhanced AMPK phosphorylation, and blunted PUN-mediated anti-oxidative effects and cardioprotection. These results indicate for the first time that PUN pretreatment protect against I/R-induced oxidative stress and myocardial injury via activation of AMPK.

Keywords: AMPK; Myocardial Ischemia/Reperfusion; Oxidative Stress; Punicalagin.

MeSH terms

  • AMP-Activated Protein Kinases / drug effects*
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Cardiotonic Agents / pharmacology
  • Coronary Vessels / surgery*
  • Creatine Kinase, MB Form / drug effects
  • Creatine Kinase, MB Form / metabolism
  • Disease Models, Animal
  • Heart / drug effects*
  • Hydrolyzable Tannins / pharmacology*
  • L-Lactate Dehydrogenase / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Ligation
  • Male
  • Myocardial Reperfusion Injury* / metabolism
  • Myocardial Reperfusion Injury* / pathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / drug effects
  • Oxidative Stress
  • Premedication*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antioxidants
  • Cardiotonic Agents
  • Hydrolyzable Tannins
  • punicalagin
  • L-Lactate Dehydrogenase
  • AMP-Activated Protein Kinases
  • Creatine Kinase, MB Form