Neuroprotective effect of punicalagin against cerebral ischemia reperfusion-induced oxidative brain injury in rats

J Stroke Cerebrovasc Dis. 2014 Nov-Dec;23(10):2869-2878. doi: 10.1016/j.jstrokecerebrovasdis.2014.07.020. Epub 2014 Oct 3.

Abstract

Background: Punicalagin (PG) is a hydrolyzable polyphenol in Punica granatum. It has been previously reported that it has a protective effect against hypoxia-induced ischemia brain injury. It is a potent antioxidant. The present study is aimed to evaluate the antioxidant potential of PG against focal cerebral ischemia-reperfusion injury in rats subjected to middle cerebral artery occlusion (MCAO).

Methods: Rats were randomly divided into sham, MCAO, PG-treated groups. PG (15 and 30 mg/kg) vehicle was administered orally for 7 days before MCAO. Rats were anesthetized with ketamine (100 mg/kg), xylazine (10 mg/kg), and subjected to 2 hours occlusion, and 22 hours reperfusion. Neurologic deficit, brain water content (BWC), histopathology changes, and oxidative stress markers were evaluated after 22 hours of reperfusion. In comparison with MCAO model group, treatment with PG significantly reduced the neurologic deficit scores and BWC.

Results: PG-attenuated neuronal damage occurred by downregulating the levels of malondialdehyde, sodium-potassium adenosine triphosphatase activity, nitric oxide, protein carbonyl content, and mitochondria-generated reactive oxygen species and upregulating the superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, glutathione reductase activities.

Conclusions: Taken together, these results suggested that supplementation of PG treatment effectively ameliorates the cerebral ischemia/reperfusion induced oxidative damage by virtue of its antioxidant potential.

Keywords: Cerebral ischemia/reperfusion injury; antioxidant; oxidative stress; punicalagin.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Biomarkers / metabolism
  • Brain / blood supply*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain Edema / prevention & control
  • Disease Models, Animal
  • Hydrolyzable Tannins / pharmacology*
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / prevention & control*
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Protein Carbonylation
  • Rats, Wistar
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Time Factors

Substances

  • Antioxidants
  • Biomarkers
  • Hydrolyzable Tannins
  • Neuroprotective Agents
  • punicalagin