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植物提取物和ω-3改善D-半乳糖模型小鼠的短期记忆并调节微生物群-肠-脑轴

Plant Extracts and ω-3 Improve Short-Term Memory and Modulate the Microbiota-Gut-Brain Axis in D-galactose Model Mice.

作者信息

Martin Marie, Boulaire Milan, Lucas Céline, Peltier Adrien, Pourtau Line, Gaudout David, Layé Sophie, Pallet Véronique, Joffre Corinne, Dinel Anne-Laure

机构信息

Université Bordeaux, INRAE, Bordeaux INP, Nutrineuro, Bordeaux, France; Activ'Inside, 12 route de Beroy, ZA du Grand Cazeau, Beychac-et-Caillau.

Université Bordeaux, INRAE, Bordeaux INP, Nutrineuro, Bordeaux, France.

出版信息

J Nutr. 2024 Dec;154(12):3704-3717. doi: 10.1016/j.tjnut.2024.09.015. Epub 2024 Sep 25.

DOI:10.1016/j.tjnut.2024.09.015
PMID:39332773
Abstract

BACKGROUND

Aging, characterized by a slow and progressive alteration of cognitive functions, is associated with gut microbiota dysbiosis, low-grade chronic inflammation, as well as increased oxidative stress and neurofunctional alterations. Some nutrients, such as polyphenols, carotenoids, and omega (ω)-3 (n-3), are good candidates to prevent age-related cognitive decline, because of their immunomodulatory, antioxidant, and neuroprotective properties.

OBJECTIVES

The objective of this study was to demonstrate the preventive effect of a combination of plant extracts (PE) containing Memophenol™ (grapes and blueberries polyphenols) and a patented saffron extract (saffron carotenoids and safranal) and ω-3 on cognitive function in a mouse model of accelerated aging and to understand the biological mechanisms involved.

METHODS

We used an accelerated-aging model by injecting 3-mo-old male C57Bl6/J mice with D-galactose for 8 wk, during which they were fed with a balanced control diet and supplemented or not with PE and/or ω-3 (n = 15-16/group). Short-term memory was evaluated by Y-maze test, following analyses of hippocampal and intestinal RNA expressions, brain fatty acid and oxylipin amounts, and gut microbiota composition (16S rRNA gene sequencing). Statistical analyses were performed (t test, analysis of variance, and Pearson correlation).

RESULTS

Our results showed that oral administration of PE, ω-3, or both (mix) prevented hippocampus-dependent short-term memory deficits induced by D-galactose (P < 0.05). This effect was accompanied by the modulation of gut microbiota, altered by the treatment. PE and the mix increased the expression of antioxidative and neurogenesis markers, such as catalase and doublecortin, in hippocampus (P < 0.05 for both). Moreover, ω-3 and the mix showed a higher ω-3 amounts (P < 0.05) and EPA-derived 18- hydroxyeicosapentaenoic acid (P < 0.001) in prefrontal cortex. These changes may contribute to the improvement in memory.

CONCLUSIONS

These results suggest that the mix of PE and ω-3 could be more efficient at attenuating age-related cognitive decline than individual supplementations because it targeted, in mice, the different pathways impaired with aging.

摘要

背景

衰老的特征是认知功能缓慢且渐进性改变,与肠道微生物群失调、低度慢性炎症以及氧化应激增加和神经功能改变有关。一些营养素,如多酚、类胡萝卜素和ω-3(n-3)脂肪酸,因其免疫调节、抗氧化和神经保护特性,是预防与年龄相关的认知衰退的良好候选物。

目的

本研究的目的是证明含有Memophenol™(葡萄和蓝莓多酚)的植物提取物(PE)与专利藏红花提取物(藏红花类胡萝卜素和藏红花醛)以及ω-3脂肪酸的组合对加速衰老小鼠模型认知功能的预防作用,并了解其中涉及的生物学机制。

方法

我们通过给3月龄雄性C57Bl6/J小鼠注射D-半乳糖8周建立加速衰老模型,在此期间,给它们喂食均衡的对照饮食,并补充或不补充PE和/或ω-3(每组n = 15 - 16只)。通过Y迷宫试验评估短期记忆,随后分析海马和肠道RNA表达、脑脂肪酸和氧化脂质含量以及肠道微生物群组成(16S rRNA基因测序)。进行了统计分析(t检验、方差分析和Pearson相关性分析)。

结果

我们的结果表明,口服PE、ω-3或两者(混合物)可预防由D-半乳糖诱导的海马依赖性短期记忆缺陷(P < 0.05)。这种作用伴随着肠道微生物群的调节,治疗使其发生改变。PE和混合物增加了海马中抗氧化和神经发生标志物(如过氧化氢酶和双皮质素)的表达(两者均P < 0.05)。此外,ω-3和混合物在前额叶皮质中显示出更高的ω-3含量(P < 0.05)和源自二十碳五烯酸(EPA)的18-羟基二十碳五烯酸(P < 0.001)。这些变化可能有助于记忆改善。

结论

这些结果表明,PE和ω-3的混合物在减轻与年龄相关的认知衰退方面可能比单独补充更有效,因为在小鼠中它针对了随着衰老而受损的不同途径。

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