1 Introduction Original article Brown propolis attenuates cerebral ischemia-induced oxidative damage via affecting antioxidant enzyme system in mice Gholamreza Bazmandegan a, d Mohammad Taher Boroushaki a, b Ali Shamsizadeh c, d Fatemeh Ayoobi c, d Elham Hakimizadeh c, d Mohammad Allahtavakoli c, d, ⁎ mohammadatir@yahoo.com (Please change to: m_alahtavakoli@rums.ac.ir) a Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran b Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran c Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran d Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran ⁎ Corresponding author : Physiology-Pharmacology Research Center, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. (please add the follwing to the end of corresponding address " P.O.Box: 7718134567, Fax: +983431315003") Abstract Oxidative stress plays a critical role in ischemic brain injury. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) are the enzymes underlying the endogenous antioxidant mechanisms affected by stroke and are considered as oxidative stress biomarkers. Brown propolis (BP) is a bioactive natural product with a set of biological activities that in turn may differ depending on the area from which the substance is originated. The aim of this study was to investigate the effect of water-extracted brown propolis (WEBPs), from two regions of Iran, against cerebral ischemia-induced oxidative injury in a mouse model of stroke. Experimentally, the chemical characterization and total polyphenol content were determined using GC/MS and Folin–Ciocalteu assay respectively. Seventy-two adult male mice were randomly divided into the surgical sham group, control group (treated with vehicle), and four groups of WEBPs-treated animals. The WEBPs were administered at the doses of 100 and 200 mg/kg IP, during four different time points. Oxidative stress biomarkers (SOD and GPx activity, SOD/GPx ratio), lipid peroxidation (LPO) index (malondialdehyde content) and infarct volume were measured 48 h post stroke. Behavioral tests were evaluated 24 and 48 h after stroke. WEBPs treatment resulted in significant restoration of antioxidant enzymes activity and a subsequent decrease in LPO as well as the infarct volume compared to the control group. Sensory-motor impairment and neurological deficits were improved significantly as well. These results indicate that Iranian BP confers neuroprotection on the stroke-induced neuronal damage via an antioxidant mechanism which seems to be mediated by the endogenous antioxidant system. Abbreviations: SOD, superoxide dismutase; GPx, glutathione peroxidase; MDA, malondialdehyde; BP, brown propolis; WEBPs, water-extracted brown propolis; LPO, lipid peroxidation; TTC,2 3 , 3, 5-triphenyltetrazolium chloride; MCA, middle cerebral artery; MCAO, middle cerebral artery occlusion; TBA, thiobarbituric acid; KhWEBP, water-extracted brown propolis from Khorasan Razavi province of Iran; KeWEBP, water-extracted brown propolis from Kerman province of Iran Keywords: Cerebral ischemia; Brown propolis; Neuroprotection; Antioxidant; Oxidative stress at