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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. [ABSTRACT FROM AUTHOR]

Abstract: The neuronal mitochondria succumb to ischemia–reperfusion injury and release huge amount of reactive oxygen species and ultimately lead the neurons to intrinsic pathway of programmed cell death (iPCD). The present study was undertaken to elucidate the ischemia–reperfusion-induced oxidative stress and molecular events in iPCD 24h post ischemia–reperfusion injury and plausible mitigation by zingerone, a potent antioxidant of ginger rhizome. The right middle cerebral artery was occluded for 2h followed by reperfusion for 22hours. A maximum infarct volume (43.29%) and mitochondrial injury (56.99%) was observed in middle cerebral artery occlusion (MCAO) group. However, zingerone administration (50 and 100mg/kg b.wt. orally twice) at 5h and 12h from initiation of MCAO showed a significant reduction in infarct volume and mitochondrial injury (p <0.001). Zingerone treatment significantly improved behavioral outputs (p <0.05) and histological architecture (p <0.001) by reducing lipid peroxidation (p <0.01), augmenting the reduced glutathione content (p <0.01) and restoring Na+-K+ ATPase and superoxide dismutase activities (p <0.01) in MCAO brain. Zingerone successfully reduced the caspase-3 and -9 activities in MCAO group (p <0.05) and succeeded in lowering the expressions of pro-apoptotic proteins — Apaf-1 and Bax (p <0.001). The present study suggests that zingerone is a potent antioxidant that salvaged the ischemic penumbral zone neurons by inhibiting iPCD and oxidative stress. [Copyright &y& Elsevier]