Please cite this article in press as: S. Umukoro, et al., Jobelyn ® ameliorates neurological deficits in rats with ischemic stroke through inhibition of release of pro-inflammatory cytokines and NF-B signaling pathway, Pathophysiology (2018), https://doi.org/10.1016/j.pathophys.2018.10.002 ARTICLE IN PRESS G Model PATPHY-973; No. of Pages 12 Pathophysiology xxx (2018) xxx–xxx Contents lists available at ScienceDirect Pathophysiology journal homepage: www.elsevier.com/locate/pathophys Jobelyn ® ameliorates neurological deficits in rats with ischemic stroke through inhibition of release of pro-inflammatory cytokines and NF-B signaling pathway Solomon Umukoro a,∗ , Ejiroghene E. Oghwere a , Benneth Ben-Azu a , Olatunde Owoeye b , Abayomi M. Ajayi a , Osarume Omorogbe a , Olajuwon Okubena c a Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria b Neurotrauma & Neuroregeneration Unit, Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria c Health Forever Products Ltd., Ikeja, Lagos, Nigeria a r t i c l e i n f o Article history: Received 29 June 2018 Received in revised form 28 September 2018 Accepted 16 October 2018 Available online xxx Keywords: Jobelyn ® Bilateral common carotid artery occlusion Ischemic stroke Oxidative stress Pro-inflammatory cytokines a b s t r a c t The effects of Jobelyn ® (JB) on neurological deficits and biochemical alterations associated with ischemic stroke induced by bilateral common carotid artery occlusion (BCCAO) in rats were investigated in this study. Male Wistar rats were divided into five groups (n = 8): group 1 served as Sham control; group 2, which served as negative control received normal saline while groups 3–5 were given JB (25, 50 and 100 mg/kg, p.o) daily for 28 days. Then, rats in groups 2–5 were subjected to BCCAO for 30 min and reperfusion afterwards. Neurological deficits were assessed 3 h post-reperfusion using a 9-point neuro- logical scoring scale. The levels of biomarkers of oxidative stress and pro-inflammatory cytokines (tumour necrotic factor- and interleukin-6), expressions of immunopositive cells of nuclear factor-kappa B (NF- B) and acetyl-cholinesterase (AChE) activity were determined in brain tissues. Histology of the striatum, prefrontal cortex (PFC) and hippocampus (CA1) was also evaluated. JB improved BCCAO-induced neuro- logical deficits and attenuated increased oxidative stress and AChE activity in rats subjected to BCCAO (p < 0.05). Increased brain levels of tumour necrotic factor- and interleukin-6 as well as expressions of immunopositive cells of NF-B were decreased by JB. JB reduced brain damage and also increased pop- ulation of viable neurons in the striatum, PFC and hippocampus of ischemic stroke rats. These findings suggest that the positive effect of JB on neurological function in rats with ischemic stroke may be related to inhibition of oxidative stress, release of pro-inflammatory cytokines and expressions of immunopositive cells of NF-B. © 2018 Elsevier B.V. All rights reserved. 1. Introduction Ischemic stroke is a fatal disease caused by sudden obstruc- tion of cerebral blood flow with subsequent neuronal cell death or tissue necrosis [1,2]. Occlusion of the blood vessels (carotid arter- ies) that supply blood to the brain and subsequent reperfusion are the critical factors involved in the pathology of ischemic stroke [3–5]. Stroke is the second leading cause of death and disability worldwide [6]. According to World Health Organization [WHO], 15 million people suffer stroke worldwide each year, with over 6 mil- lion dying and more than half of the survivors being permanently disabled [7]. The death rate due to the disease in most African coun- ∗ Corresponding author. E-mail address: umusolo@yahoo.com (S. Umukoro). tries is quite alarming resulting in huge loss of economic manpower and productivity [8,9]. Moreover, stroke is typically associated with neurological deficits and the belief that the disease is incurable even contributes to a wide range of psychiatric disturbances such as anxiety, depression and memory deficits [10]. Over the past few decades, the understanding of the pathophys- iology of stroke has increased but little progress has been made in the development of effective drugs for treatment of this debilitat- ing disease [4; 7]. Current approach to the management of stroke focuses on the amelioration of symptoms as cure for the disease still remains elusive [4; 7]. The clinical efficacy of tissue plasmino- gen activators currently used for stroke has been compromised by serious adverse effects [11,12]. Also, the need to administer them as quick as possible, at least within 3 h after onset of symptoms of the disease makes it almost unrealistic for patients in most African communities to benefit from these drugs [11,12]. Moreover, the https://doi.org/10.1016/j.pathophys.2018.10.002 0928-4680/© 2018 Elsevier B.V. All rights reserved.