Perillyl alcohol improves functional and histological outcomes against ischemia-reperfusion injury by attenuation of oxidative stress and repression of COX-2, NOS-2 and NF-κB in middle cerebral artery occlusion rats

Fakhrul Islam, Rizwana Tabassum, Kumar Vaibhav, Pallavi Shrivastava, Andleeb Khan, Mohd Ejaz Ahmed, Mohammad Ashafaq, Mohammad Badruzzaman Khan, Farah Islam, Mohammed M. Safhi

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Perillyl alcohol (PA) is a monoterpene found in essential oils of mints, cherries, citreous fruits and lemon grass, reported to have antioxidant and anti-inflammatory properties. However, the role of PA in stroke is still illusive. Since oxidative stress and inflammation play a pivotal role in ischemia-reperfusion (I-R) injury, this study was designed to elucidate the potential effects of PA against I-R induced pathology in rat's brain. Middle cerebral artery occlusion (MCAO) for 2 h followed by 22 h reperfusion in Wistar male rats (250-280 g, 14-16 weeks old) induced the behavioral and histological alterations along with exhausted antioxidant status and enhanced inflammatory mediators. However, PA administration (25, 50 and 100 mg/kg b.wt orally once daily for 7 days) prior to MCAO significantly attenuated neurological deficits related to flexion test and spontaneous motor activity, improved grip strength and motor coordination in a dose dependent manner. PA treatment also inhibited oxidative stress in MCAO rats as evident from decreased lipid peroxidation and augmented level of reduced glutathione and restored activities of catalase, glutathione peroxidase, and glutathione reductase and thus, reduced infarct volume and protected the brain histology after I-R injury. Furthermore, PA markedly suppressed the level of proinflammatory cytokines (IL-1β, TNF α and IL-6) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS-2) and nuclear factor κB (NF-κB) in MCAO group. In conclusion, PA mediates neuroprotection against I-R injury via mitigation of oxidative stress and inflammation and thus, may be a good therapeutic approach in stroke prone patient.

Original languageEnglish (US)
Pages (from-to)190-199
Number of pages10
JournalEuropean Journal of Pharmacology
Volume747
DOIs
StatePublished - Jan 15 2015

Keywords

  • Behavior
  • Inflammation
  • Ischemia-reperfusion
  • Middle cerebral artery occlusion
  • Oxidative stress
  • Perillyl alcohol

ASJC Scopus subject areas

  • Pharmacology

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