Department of Neurology, Icahn School of Medicine at Mount Sinai New York, NY, USA ; Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center Bronx, NY, USA.
Department of Neurology, Icahn School of Medicine at Mount Sinai New York, NY, USA.
Front Aging Neurosci. 2014 Mar 14;6:42. doi: 10.3389/fnagi.2014.00042. eCollection 2014.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol, and Concord grape juice extract), with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ) mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ)-induced long term potentiation (LTP) deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.
阿尔茨海默病（AD）是最常见的与衰老相关的神经退行性疾病，目前尚无治愈方法。其发病和进展受多种因素影响。越来越多的人认为，成功的治疗将依赖于同时针对 AD 的多种病理特征。多酚化合物具有许多已被证实的健康益处。在这项研究中，我们检验了这样一个假设，即结合三种多酚制剂（葡萄籽提取物、白藜芦醇和康科德葡萄汁提取物），它们具有不同的多酚组成和部分冗余的生物活性，可能同时协同减轻 AD 小鼠模型中淀粉样蛋白-β（Aβ）介导的神经病理学和认知障碍。我们发现，多酚联合给药不会改变大脑中生物活性多酚代谢物的特征。我们还发现，与单独治疗相比，联合治疗在 J20 AD 小鼠中对认知障碍有更好的保护作用。电生理检查表明，从这些多酚中提取的一些脑穿透性多酚代谢物的急性处理可改善寡聚体 Aβ（oAβ）诱导的海马切片长时程增强（LTP）缺陷。此外，我们发现联合治疗后大脑中的总淀粉样蛋白含量大大降低。我们的研究提供了实验证据，表明针对多种疾病机制的多酚的应用可能更有可能产生治疗效果。
