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      Schizandrin, an Antioxidant Lignan from Schisandra chinensis, Ameliorates A β 1–42-Induced Memory Impairment in Mice

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          Abstract

          In the present study, we examined the effect of schisandrin (SCH) of Schisandra chinensis on the amyloid-beta 1–42- (A β 1–42-) induced memory impairment in mice and elucidated the possible antioxidative mechanism. Mice were intracerebroventricular (i.c.v.) injected with the aggregated A β 1–42 and then treated with SCH (4, 12, and 36 mg/kg body weight) or donepezil (DPZ), a reference drug (0.65 mg/kg) by intragastric infusion for 14 days. Noncognitive disturbances and cognitive performance were evaluated by locomotor activity test, Y-maze test, and water maze test. Antioxidative enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and levels of malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG) within the cerebral cortex and hippocampus of mice were measured to elucidate the mechanism. Our results showed that SCH significantly improved A β 1–42-induced short-term and spatial reference memory impairments in Y-maze test and water maze test. Furthermore, in the cerebral cortex and hippocampus of mice, SOD and GSH-px activities, GSH level, and GSH/GSSG ratio were increased, and levels of MDA and GSSG were decreased by the treatment of SCH. These results suggest that SCH is a potential cognitive enhancer against Alzheimer's disease through antioxidative action.

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          Most cited references61

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          Mechanisms of neuronal degeneration in Alzheimer's disease.

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            Neuroprotective strategies involving ROS in Alzheimer disease.

            Alzheimer disease (AD) is a neurodegenerative disorder in which oxidative stress is a key hallmark. It occurs early in disease pathogenesis and can exacerbate its progression. Several causes of oxidative stress have been determined over the years. First, mitochondria play an important role in the generation and accumulation of free radicals. In addition to mitochondria, inflammation can also induce oxidative damage, especially via microglia, and microglia are also important for Aβ clearance. In AD, both mitochondrial function and inflammatory response are affected, leading to increased ROS formation and oxidative damage to lipid, proteins, and nucleic acids. Some other sources have also been identified. From these findings, various neuroprotective strategies against ROS-mediated damages have been elaborated in AD research. This review recapitulates some of the major strategies used to prevent oxidative stress and disease progression. Outcomes from in vitro and in vivo studies using models of AD are encouraging. However, only a few clinical trials have provided positive results in terms of slowing down cognitive decline. Nonetheless, there is still hope for improved compounds that would better target pathways implicated in ROS production. In fact, facilitating the endogenous antioxidant system by modulating transcription has great promise for AD therapy. Published by Elsevier Inc.
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              Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer's disease.

              Alzheimer's disease (AD) is a late-onset dementia that is characterized by the loss of memory and an impairment of multiple cognitive functions. Advancements in molecular, cellular, and animal model studies have revealed that the formation of amyloid beta (Abeta) and other derivatives of the amyloid precursor protein (APP) are key factors in cellular changes in the AD brain, including the generation of free radicals, oxidative damage, and inflammation. Recent molecular, cellular, and gene expression studies have revealed that Abeta enters mitochondria, induces the generation of free radicals, and leads to oxidative damage in post-mortem brain neurons from AD patients and in brain neurons from cell models and transgenic mouse models of AD. In the last three decades, tremendous progress has been made in mitochondrial research and has provided significant findings to link mitochondrial oxidative damage and neurodegenerative diseases such as AD. Researchers in the AD field are beginning to recognize the possible involvement of a mutant APP and its derivatives in causing mitochondrial oxidative damage in AD. This article summarizes the latest research findings on the generation of free radicals in mitochondria and provides a possible model that links Abeta proteins, the generation of free radicals, and oxidative damage in AD development and progression.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OXIMED
                Oxidative Medicine and Cellular Longevity
                Hindawi Publishing Corporation
                1942-0900
                1942-0994
                2012
                4 July 2012
                : 2012
                : 721721
                Affiliations
                1Department of Pharmacognosy, Shenyang Pharmaceutical University, Shenyang 110016, China
                2National Population and Family Planning Key Laboratory of Contraceptives Drugs & Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China
                3Pharmacy College, Jinan University, Guangzhou 510632, China
                Author notes

                Academic Editor: David Vauzour

                Article
                10.1155/2012/721721
                3399599
                22829961
                4c28fc52-2d52-4be0-9680-220359ec2eab
                Copyright © 2012 Di Hu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 March 2012
                : 14 May 2012
                : 14 May 2012
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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