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      Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia

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          Abstract

          Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson's disease, cerebral ischemia and Alzheimer's disease. However, its effects on vascular dementia remain unclear. The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion. At 8–12 weeks after model induction, rats were intragastrically administered 25 mg/kg resveratrol daily. Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze, and prolonged the time spent percentage and swimming distance percentage in the target quadrant during the probe test, indicating that resveratrol improved learning and memory ability in vascular dementia rats. Further experiments found that resveratrol decreased malonyldialdehyde levels, and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats. These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.

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          SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.

          A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.
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            Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides.

            Several epidemiological studies indicate that moderate consumption of wine is associated with a lower incidence of Alzheimer's disease. Wine is enriched in antioxidant compounds with potential neuroprotective activities. However, the exact molecular mechanisms involved in the beneficial effects of wine intake on the neurodegenerative process in Alzheimer's disease brain remain to be clearly defined. Here we show that resveratrol (trans-3,4',5-trihydroxystilbene), a naturally occurring polyphenol mainly found in grapes and red wine, markedly lowers the levels of secreted and intracellular amyloid-beta (Abeta) peptides produced from different cell lines. Resveratrol does not inhibit Abeta production, because it has no effect on the Abeta-producing enzymes beta- and gamma-secretases, but promotes instead intracellular degradation of Abeta via a mechanism that involves the proteasome. Indeed, the resveratrol-induced decrease of Abeta could be prevented by several selective proteasome inhibitors and by siRNA-directed silencing of the proteasome subunit beta5. These findings demonstrate a proteasome-dependent anti-amyloidogenic activity of resveratrol and suggest that this natural compound has a therapeutic potential in Alzheimer's disease.
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              Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease.

              Resveratrol, a polyphenol found in red wine, peanuts, soy beans, and pomegranates, possesses a wide range of biological effects. Since resveratrol's properties seem ideal for treating neurodegenerative diseases, its ability to diminish amyloid plaques was tested. Mice were fed clinically feasible dosages of resveratrol for forty-five days. Neither resveratrol nor its conjugated metabolites were detectable in brain. Nevertheless, resveratrol diminished plaque formation in a region specific manner. The largest reductions in the percent area occupied by plaques were observed in medial cortex (-48%), striatum (-89%) and hypothalamus (-90%). The changes occurred without detectable activation of SIRT-1 or alterations in APP processing. However, brain glutathione declined 21% and brain cysteine increased 54%. The increased cysteine and decreased glutathione may be linked to the diminished plaque formation. This study supports the concept that onset of neurodegenerative disease may be delayed or mitigated with use of dietary chemo-preventive agents that protect against beta-amyloid plaque formation and oxidative stress.
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                Author and article information

                Journal
                Neural Regen Res
                Neural Regen Res
                NRR
                Neural Regeneration Research
                Medknow Publications & Media Pvt Ltd (India )
                1673-5374
                1876-7958
                05 August 2013
                : 8
                : 22
                : 2050-2059
                Affiliations
                [1 ] Department of Neurology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
                [2 ] Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450002, Henan Province, China
                Author notes

                Xingrong Ma, Master, Attending physician.

                Xingrong Ma and Zhikun Sun contributed equally to this article.

                Corresponding author: Boai Zhang, Chief physician, Department of Neurology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China zhangboaidoctor@ 123456163.com ; Jiewen Zhang, Chief physician, Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450002, Henan Province, China, zhangjiewen9900@ 123456126.com (N201301009)

                Author contributions: Ma XR conceived and designed this study. Sun ZK and Jia YJ conducted the experiments, and collected and analyzed the data. Liu YR wrote the manuscript. Zhang BA and Zhang JW revised the manuscript. All authors approved the final version of the paper.

                Author statements: The manuscript is original, has not been submitted to or is not under consideration by another publication, has not been previously published in any language or any form, including electronic, and contains no disclosure of confidential information or authorship/patent application disputations.

                Article
                NRR-8-2050
                10.3969/j.issn.1673-5374.2013.22.004
                4146064
                25206513
                6a191c6f-4a7b-4037-9faf-636c75addec9
                Copyright: © Neural Regeneration Research

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 April 2013
                : 02 June 2013
                Categories
                Research and Report Article: Traditional Chinese Medicine and Neural Regeneration

                neural regeneration,traditional chinese medicine,resveratrol,vascular dementia,cognitive function,learning and memory,oxidative stress,bilateral common carotid,artery occlusion,malonyldialdehyde,superoxide dismutase,neuroregeneration

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