HYPERICUM PERFORATUM IMPROVE MEMORY AND LEARNING IN ALZHEIMER'S MODEL: (EXPERIMENTAL STUDY IN MICE) Original Article KHAYRA ZERROUKI a,b* , NOUREDDINE DJEBLI a , ESRA EROGLU OZKAN c , NURTEN OZSOY d , OZHAN GUL e , AFIFE MAT c a Laboratory of Pharmacognosy and Api-Phytotherapy Department of Biology FSNV-Mostaganem University, Mostaganem, Algeria, b Department of Biology-Faculty of Naturaal and Life Sciences Chlef University, c Department of Pharmacognosy Faculty of Pharmacy- Istanbul Istanbul, d Department of Biochemistry, Faculty of Pharmacy, e Received: 05 Jul 2015 Revised and Accepted: 20 May 2016 Department of Pharmaceutical Toxicology Faculty of Pharmacy, Istanbul University, Istanbul, Turkey Email: soumaia9@gmail.com ABSTRACT Objective: The aim of this study, we based on protective and antioxidant efficiency of Hypericum perforatum that shows a wide range of beneficial effect in vitro and in vivo. Methods: The in vitro antioxidant activity of the extract was assessed by using several antioxidant tests. The cytotoxic activity of Hypericum perforatum was also determined by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide viability assay on ordinary used cell lines. In vivo experiments in Swiss mice were determined by performing behavioral, memory tests and histological study. According to tests results, H. perforatum may be relevant to the treatment of cognitive disorders. Results: The results of chemical analysis showed a hight level of hyperforin and quercitin that had an important antioxidant activity proved in vitro with the 2, 2-diphenyl-1-picrylhydrazyl, Anti-lactoperoxidase and superoxide dismutases; this antioxidant activity was confirmed in vivo after the non-toxic results by means of improvement in behavioral and memory than the reducing shrunken in pyramidal cells of mice brains. Conclusion: The present study suggests that Hypericum perforatum modulate the oxidative stress and be involved in the protective effect against oxidative damage and neurodegenerative diseases in mice. Keywords: Neurotoxicity, Alzheimer’s disease, Phytotherapy, Hypericum perforatum, Neuroprotective, Mice © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) INTRODUCTION Alzheimer's disease (AD) is a multifactorial disease, complex, and progressive affecting the older population the most observed dementia cases is in persons over 65 y of age [1, 2]. Histological and pathological studies of AD have revealed that multiple cellular pathways are involved in AD progression [3]. The pathological features identified in the central nervous system (CNS) in AD are amyloid plaques, neurofibrillary tangles, inflammatory processes and disturbance of neurotransmitters [4, 5]. The dysfunction and degeneration of synapses in AD may involve Aβ- induced oxidative stress compromises the mitochondrial function by an oxidative-stress-mediated mechanism [6]. Reactive oxygen species (ROS) are produced by many redox processes that normally occur in the metabolism of aerobic cells. These species are very reactive and harmful to the cells. If not eliminated, ROS can damage vital molecules, such as proteins, DNA, and lipids. Cells express several defense mechanisms, including antioxidant enzymes and non-enzymatic compounds that help prevent the damaging effects of ROS [7]. Oxidative stress can also play an important role in the development of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases [8, 9]. There is an increasing interest in natural antioxidants, namely the phenols, present in medicinal and dietary plants, that might help prevent oxidative damage. [10-14]. In situations of increased free radical generation, the reinforcement of endogenous antioxidants via intake of dietary antioxidants may be of particular importance in attenuating the cumulative effects of oxidatively damaged molecules. In recent years, the consumption of Hypericum perforatum (St. John’s wort) derived products have increased dramatically, and presently it is one of the most consumed medicinal plants over the world [15]. The commercially available H. perforatum derived products include sophisticated phytopharmaceuticals and nutraceuticals, teas, tinctures, juices and oil macerates [16]. H. perforatum has a wide range of medicinal applications, including skin wounds, eczema, burns, diseases of the alimentary tract and psychological disorders. Nowadays, its use in the treatment of mild to moderate depression has become prominent [17-19]. Numerous papers have been published concerning these aspects and several recent reviews can be pointed out [19-21]. In spite of this intense research activity, the antioxidant potential of H. perforatum extracts has been somewhat neglected. Current studies suggested that H. perforatum possessed protective effects against H2 O2 The chemical composition of the Hypericum species is composed of naphthodianthrones (especially hypericin and pseudo hypericin), acylphloroglucinol derivatives (especially hyperforin and adhyperforin), flavonoids (especially quercetin, quercitrin, hyperoside and biapigenin), tannins, n-alkanes, xanthones and essential oils. [18, 23, 24] induced apoptosis of PC12 cells than might be useful in the treatment of oxidative stress related to neurodegenerative diseases such as Alzheimer disease [22]. The aim of this study was to identify the potential of H. perforatum as a protective and therapeutic agent against neurodegenerative disorders and Alzheimer's disease. The chemical composition of ethanolic extract of H. perforatum was analyzed by using HPLC-DAD. In order to determine the antioxidant potential of H. perforatum, was evaluated by employing several antioxidant tests. The cytotoxic activity of the extract was also determined by using MTT cell cytotoxicity screening assay on HeLa and NRK-52E cell lines. The in vivo studies on Swiss male mice were determined by utilizing behavioral, memory tests and histological analysis. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 8, 2016