Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats

Life Sci. 2014 Aug 21;110(2):61-9. doi: 10.1016/j.lfs.2014.06.023. Epub 2014 Jul 8.

Abstract

Aim: Interruption to blood flow causes ischemia and infarction of brain tissues with consequent neuronal damage and brain dysfunction. Pomegranate extract is well tolerated, and safely consumed all over the world. Interestingly, pomegranate extract has shown remarkable antioxidant and anti-inflammatory effects in experimental models. Many investigators consider natural extracts as novel therapies for neurodegenerative disorders. Therefore, this study was carried out to investigate the protective effects of standardized pomegranate extract against cerebral ischemia/reperfusion-induced brain injury in rats.

Main methods: Adult male albino rats were randomly divided into sham-operated control group, ischemia/reperfusion (I/R) group, and two other groups that received standardized pomegranate extract at two dose levels (250, 500 mg/kg) for 15 days prior to ischemia/reperfusion (PMG250+I/R, and PMG500+I/R groups). After I/R or sham operation, all rats were sacrificed and brains were harvested for subsequent biochemical analysis.

Key findings: Results showed reduction in brain contents of MDA (malondialdehyde), and NO (nitric oxide), in addition to enhancement of SOD (superoxide dismutase), GPX (glutathione peroxidase), and GRD (glutathione reductase) activities in rats treated with pomegranate extract prior to cerebral I/R. Moreover, pomegranate extract decreased brain levels of NF-κB p65 (nuclear factor kappa B p65), TNF-α (tumor necrosis factor-alpha), caspase-3 and increased brain levels of IL-10 (interleukin-10), and cerebral ATP (adenosine triphosphate) production. Comet assay showed less brain DNA (deoxyribonucleic acid) damage in rats protected with pomegranate extract.

Significance: The present study showed, for the first time, that pre-administration of pomegranate extract to rats, can offer a significant dose-dependent neuroprotective activity against cerebral I/R brain injury and DNA damage via antioxidant, anti-inflammatory, anti-apoptotic and ATP-replenishing effects.

Keywords: ATP; Caspase-3; Cerebral ischemia/reperfusion; Comet assay; GPX; GRD; IL-10; MDA; NF-κB p65; Pomegranate extract; SOD; TNF-α.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Analysis of Variance
  • Animals
  • Brain Ischemia / prevention & control*
  • Caspase 3 / metabolism
  • Comet Assay
  • DNA Damage / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Interleukin-10 / metabolism
  • Lythraceae / chemistry*
  • Male
  • Malondialdehyde / metabolism
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology*
  • Phytotherapy / methods*
  • Plant Extracts / pharmacology*
  • Rats
  • Reperfusion Injury / prevention & control*
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • Neuroprotective Agents
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Malondialdehyde
  • Adenosine Triphosphate
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Caspase 3