As components of the Mediterranean diet (MedDiet) olive polyphenols may play a crucial role for the prevention of Alzheimer's disease (AD). Since mitochondrial dysfunction is involved in both, brain ageing and early AD, effects of 10 different purified phenolic secoiridoids (hydroxytyrosol, tyrosol, oleacein, oleuroside, oleuroside aglycon, oleuropein, oleocanthal, ligstroside, ligstroside aglycone and ligustaloside B) and two metabolites (the plant metabolite elenolic acid and the mammalian metabolite homovanillic acid) were tested in very low doses on mitochondrial function in SH-SY5Y-APP695 cells - a cellular model of early AD. All tested secoiridoids significantly increased basal ATP levels in SY5Y-APP695 cells. Oleacein, oleuroside, oleocanthal and ligstroside showed the highest effect on ATP levels and were additionally tested on mitochondrial respiration. Only oleocanthal and ligstroside were able to enhance the capacity of respiratory chain complexes. To investigate their underlying molecular mechanism, the expression of genes associated with mitochondrial biogenesis, respiration and antioxidative capacity (PGC1-α, SIRT1, CREB1, NRF1, TFAM, complex I, IV and V, GPx1, SOD2, CAT) were determined using RT-PCR. Exclusively ligstroside increased mRNA expression of SIRT1, CREB1, complex I, and GPx1. Furthermore, oleocanthal but not ligstroside decreased Aβ 1-40 levels in SH-SY5Y-APP695 cells. To investigate the in vivo effects of purified secoiridoids, the two most promising compounds (oleocanthal and ligstroside) were tested in a mouse model of ageing. Female NMRI mice, aged 12 months, received a diet supplemented with 50 mg/kg diet oleocanthal or ligstroside for 6 months (equivalent to 6.25 mg/kg b.w.). Young (3 months) and aged (18 months) mice served as controls. Ligstroside fed mice showed improved spatial working memory. Furthermore, ligstroside restored brain ATP levels in aged mice and led to a significant life extension compared to aged control animals. Our findings indicate that purified ligstroside has outstanding performance on mitochondrial bioenergetics in models of early AD and brain ageing by mechanisms that may not interfere with Aβ production. Additionally, ligstroside expanded the lifespan in aged mice and enhanced cognitive function.

中文翻译：

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在早期的阿尔茨海默氏病和脑衰老模型中，纯化的油橄榄酚和皂甙具有预防线粒体功能障碍的作用。

橄榄多酚作为地中海饮食（MedDiet）的成分，可能在预防阿尔茨海默氏病（AD）中起关键作用。由于线粒体功能障碍与大脑衰老和早期AD均有关，因此有10种不同的纯化酚类类脂类化合物（羟基酪醇，酪醇，油酸甘油酯，油苷，油苷糖苷，橄榄苦苷，油橄榄黄酮，木脂苷，木脂苷糖苷和脂木苷）的作用在非常低的剂量下，对SH-SY5Y-APP695细胞（早期AD的细胞模型）中的线粒体功能测试了植物代谢产物亚硒酸和哺乳动物代谢产物高香草酸）。在SY5Y-APP695细胞中，所有测试的类胡萝卜素均显着增加了基础ATP水平。油脂油，橄榄苦甙，油橄榄和皂甙对ATP水平显示出最高的作用，并且还针对线粒体呼吸进行了测试。只有油藤黄和皂甙具有增强呼吸链复合物能力的能力。为了研究其潜在的分子机制，使用RT测定与线粒体生物发生，呼吸和抗氧化能力相关的基因（PGC1-α，SIRT1，CREB1，NRF1，TFAM，复合物I，IV和V，GPx1，SOD2，CAT）的表达。 -PCR。麦角苦苷仅增加SIRT1，CREB1，复合物I和GPx1的mRNA表达。此外，油烟碱而不是香脂苷降低SH-SY5Y-APP695细胞中的Aβ1-40水平。为了研究纯化的类蛇药苷的体内作用，在衰老的小鼠模型中测试了两种最有希望的化合物（油藤黄和皂甙）。NMRI雌性小鼠 年龄为12个月大的人，接受6个月补充50毫克/千克饮食的油橄榄或香脂甙饮食（相当于6.25毫克/千克体重）。幼鼠（3个月）和老年（18个月）小鼠作为对照。饲喂Ligstroside的小鼠显示出改善的空间工作记忆。此外，与老年对照组动物相比，麦冬皂苷能恢复老年小鼠的大脑ATP水平，并显着延长了寿命。我们的发现表明，提纯的木香皂苷在早期AD和脑衰老模型中对线粒体生物能学的表现出色，其机制可能不干扰Aβ的产生。此外，香脂甙可延长衰老小鼠的寿命并增强认知功能。幼鼠（3个月）和老年（18个月）小鼠作为对照。饲喂Ligstroside的小鼠显示出改善的空间工作记忆。此外，与老年对照组动物相比，麦冬皂苷能恢复老年小鼠的大脑ATP水平，并显着延长了寿命。我们的发现表明，提纯的木香皂苷在早期AD和脑衰老模型中对线粒体生物能学的表现出色，其机制可能不干扰Aβ的产生。此外，香脂甙可延长衰老小鼠的寿命并增强认知功能。幼鼠（3个月）和老年（18个月）小鼠作为对照。饲喂Ligstroside的小鼠显示出改善的空间工作记忆。此外，与老年对照组动物相比，麦冬皂苷能恢复老年小鼠的大脑ATP水平，并显着延长了寿命。我们的发现表明，提纯的木香皂苷在早期AD和脑衰老模型中对线粒体生物能学的表现出色，其机制可能不干扰Aβ的产生。此外，香脂甙可延长衰老小鼠的寿命并增强认知功能。我们的发现表明，提纯的木香皂苷在早期AD和脑衰老模型中对线粒体生物能学具有出色的表现，其机制可能不干扰Aβ的产生。此外，香脂甙可延长衰老小鼠的寿命并增强认知功能。我们的发现表明，提纯的木香皂苷在早期AD和脑衰老模型中对线粒体生物能学具有出色的表现，其机制可能不干扰Aβ的产生。此外，香脂甙可延长衰老小鼠的寿命并增强认知功能。