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在阿尔茨海默病转基因模型中,白藜芦醇膳食补充剂可减轻斑块病理变化。

Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease.

作者信息

Karuppagounder Saravanan S, Pinto John T, Xu Hui, Chen Huan-Lian, Beal M Flint, Gibson Gary E

机构信息

Department of Neurology and Neurosciences, Weill Medical College of Cornell University, Burke Medical Research Institute, 785 Mamaroneck Ave., White Plains, NY 10605, United States.

出版信息

Neurochem Int. 2009 Feb;54(2):111-8. doi: 10.1016/j.neuint.2008.10.008. Epub 2008 Nov 8.

Abstract

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.

摘要

白藜芦醇是一种存在于红酒、花生、大豆和石榴中的多酚,具有广泛的生物学效应。由于白藜芦醇的特性似乎非常适合治疗神经退行性疾病,因此对其减少淀粉样斑块的能力进行了测试。给小鼠喂食临床上可行剂量的白藜芦醇,持续45天。在大脑中未检测到白藜芦醇及其共轭代谢产物。然而,白藜芦醇以区域特异性方式减少了斑块形成。在大脑内侧皮质(-48%)、纹状体(-89%)和下丘脑(-90%)观察到斑块所占面积百分比的最大降幅。这些变化发生时,未检测到SIRT-1的激活或APP加工过程的改变。然而,脑内谷胱甘肽下降了21%,脑内半胱氨酸增加了54%。半胱氨酸增加和谷胱甘肽减少可能与斑块形成减少有关。这项研究支持这样一种观点,即使用能够预防β-淀粉样斑块形成和氧化应激的饮食化学预防剂,可能会延迟或减轻神经退行性疾病的发病。

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