Original article Therapeutic impact of grape leaves polyphenols on certain biochemical and neurological markers in AlCl 3 -induced Alzheimer’s disease Ibrahim H. Borai a , Magda K. Ezz a , Maha Z. Rizk b , Hanan F. Aly b , Mahmoud El-Sherbiny b , Azza A. Matloub c , Ghadha I. Fouad b, * a Biochemistry Department, Faculty of Science, Ain-Shams University, Cairo, Egypt b Therapeutical Chemistry Department, National Research Center, Dokki, Cairo, Egypt c Pharmacognosy Department, National Research Center, Dokki, Cairo, Egypt A R T I C L E I N F O Article history: Received 14 April 2017 Received in revised form 27 June 2017 Accepted 6 July 2017 Keywords: Vitis vinifera Polyphenols Aluminum Alzheimer’s disease AD-rats T-maze A B S T R A C T Alzheimer’s disease (AD) is a grave and prevailing neurodegenerative disease, characterized by slow and progressive neurodegeneration in different brain regions. Aluminum (Al) is a potent and widely distributed neurotoxic metal, implicated in the neuropathogenesis of AD. This study aimed to evaluate the possible neurorestorative potential of Vitis vinifera Leaves Polyphenolic (VLP) extract in alleviating aluminum chloride (AlCl 3 )-induced neurotoxicity in male rats. AlCl 3 neurotoxicity induced a significant decrease in brain/serum acetylcholine (ACh) contents and serum dopamine (DA) levels, along with a significant increment of brain/serum acetylcholinesterase (AChE) activities. In addition, Al treatment resulted in significantly decreased serum levels of both total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF), and significantly increased serum levels of both interleukin-6 (IL-6) and total homocysteine (tHcy), as compared to control. Behavioral alterations, assessed by the T-maze test, showed impaired cognitive function. Furthermore, AD-brains revealed an increase in DNA fragmentation as evidenced by comet assay. AlCl 3 induction also caused histopathological alterations in AD-brain. Treatment of AD-rats with VLP extract (100 mg/kg body weight/day) improved neurobehavioral changes, as evidenced by the improvement in brain function, as well as, modulation of most biochemical markers, and confirmed by T-maze test, the histopathological study of the brain and comet assay. The current work indicates that the VLP extract has neuroprotective, antioxidative, anti-inflammatory, and anti-amnesic activities against AlCl 3 -induced cerebral damages and neurocognitive dysfunction. © 2017 Elsevier Masson SAS. All rights reserved. 1. Introduction Alzheimer disease (AD) is the most common neurodegenerative disorder affecting the elderly with cumulative neurocognitive decline and memory impairment (dementia). Multiple pathogenic factors of AD involve amyloid-b (Ab) plaques, neurofibrillary tangles (NFTs), cholinergic dysfunction and oxidative stress [1]. Accounting for about 60 to 80% of dementia cases in the elderly populations; AD has become one of the major global health challenges of the century [2]. During ageing, humans and animals show a decline in motor and cognitive functions, that could be attributed to increased susceptibility to the cumulative effects of oxidative stress and inflammation [3]. The glutamatergic pyramidal neurons in brain are highly vulnerable to deterioration in both age-associated and AD-induced cognitive impairment [4]. Abbreviations: VLP, Vitis vinifera leaves polyphenols; ACh, acetylcholine; DA, dopamine; AChE, acetylcholinesterase; TAC, total antioxidant capacities; BDNF, brain-derived neurotrophic factor; IL-6, interleukin-6; Ab, amyloid-b; NFTs, neurofibrillary tangles; AD, Alzheimer’s disease; NMR, Nuclear magnetic reso- nance; RIVA, rivastigmine; EDTA, ethylene-diamine-tetra-acetic acid; SCGE, single cell gel electrophoresis; CTL, comet tail length; TM, Tail moment; TE, Trolox equivalent; CE, catechin equivalent; GAE, gallic acid equivalent; DPPH, 2,2- diphenyl-1-picrylhydrazyl; MAO, monoamine oxidase. * Corresponding author at: Assistant Researcher in Therapeutical Chemistry Department, National Research Center (NRC), 33 El-Bohouth Street, P.O. 12622, Dokki, Cairo, Egypt. E-mail addresses: ibrahim_boraay@sci.asu.edu.eg (I.H. Borai), mkezz64@yahoo.com (M.K. Ezz), maha_zaki_rizk@yahoo.com (M.Z. Rizk), hanan_abduallah@yahoo.com (H.F. Aly), dr_elsherbiny1@yahoo.com (M. El-Sherbiny), matlouba2002@hotmail.com (A.A. Matloub), ghadhaibrahim@yahoo.com (G.I. Fouad). http://dx.doi.org/10.1016/j.biopha.2017.07.038 0753-3322/© 2017 Elsevier Masson SAS. All rights reserved. Biomedicine & Pharmacotherapy 93 (2017) 837–851 Available online at ScienceDirect www.sciencedirect.com