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葡萄提取物可保护线粒体免受氧化损伤,改善运动功能障碍,并延长帕金森病果蝇模型的寿命。

Grape extract protects mitochondria from oxidative damage and improves locomotor dysfunction and extends lifespan in a Drosophila Parkinson's disease model.

机构信息

Institute of Mitochondrial Biology and Medicine, Department of Biology and Engineering, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University School of Life Science and Technology, Xi'an, China.

出版信息

Rejuvenation Res. 2009 Oct;12(5):321-31. doi: 10.1089/rej.2009.0877.

DOI:10.1089/rej.2009.0877
PMID:19929256
Abstract

A botanical extract (Regrapex-R) prepared from whole grape (Vitis vinifera) and Polygonum cuspidatum, which contains polyphenols, including flavans, anthocyanins, emodin, and resveratrol, exhibited dose-dependent scavenging effects on reactive oxygen species (ROS). The extract inhibited increases of ROS and protein carbonyl in isolated rat liver mitochondria following exposure to 2,2'-azobis (2-amidino propane) dihydrocholoride (AAPH), a potent lipid oxidant generator. The antioxidant effects of this extract were further demonstrated by protecting enzyme activities of the mitochondrial respiratory electron transport chain (complexes I and II) and pyruvate dehydrogenase in isolated liver mitochondria with AAPH insult. In human neuroblastoma cells (SKN-MC), pretreatment of extract protected cells against AAPH induced oxidation in maintaining cell viability and inhibiting excessive ROS generation. Extract was fed to transgenic Drosophila expressing human alpha-synuclein. This model for Parkinson disease recapitulates essential features of the disorder, including loss of dopaminergic neurons in the substantia nigra and a locomotor dysfunction that is displayed by a progressive loss of climbing ability measured using a geotaxis assay. Male transgenic flies fed the extract (0.16-0.64 mg/100 g of culture medium) showed a significant improvement in climbing ability compared to controls. Female transgenic flies showed a significant extension in average lifespan. These results suggest that Regrapex-R is a potent free radical scavenger, a mitochondrial protector, and a candidate for further studies to assess its ability to protect against neurodegenerative disease and potentially extend lifespan.

摘要

一种从整颗葡萄(Vitis vinifera)和虎杖中提取的植物提取物(Regrapex-R),含有多酚类物质,包括类黄酮、花青素、大黄素和白藜芦醇,对活性氧(ROS)具有剂量依赖性的清除作用。该提取物可抑制 2,2'-偶氮双(2-脒基丙烷)二盐酸盐(AAPH)诱导的大鼠肝线粒体中 ROS 和蛋白质羰基的增加,AAPH 是一种有效的脂质氧化剂生成剂。该提取物的抗氧化作用进一步通过保护 AAPH 损伤的分离肝线粒体中的线粒体呼吸电子传递链(复合物 I 和 II)和丙酮酸脱氢酶的酶活性来证明。在人神经母细胞瘤细胞(SKN-MC)中,提取物预处理可防止 AAPH 诱导的氧化,维持细胞活力并抑制过多的 ROS 生成。提取物被喂食到表达人α-突触核蛋白的转基因果蝇中。这种帕金森病模型再现了该疾病的基本特征,包括黑质中多巴胺能神经元的丧失和运动功能障碍,这通过使用地理定向测定法测量的攀爬能力的逐渐丧失来显示。喂食提取物(0.16-0.64 mg/100 g 培养基)的雄性转基因果蝇的攀爬能力与对照组相比有显著改善。雌性转基因果蝇的平均寿命有显著延长。这些结果表明,Regrapex-R 是一种有效的自由基清除剂、线粒体保护剂,并且是进一步研究其预防神经退行性疾病和潜在延长寿命能力的候选物。

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