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Sesamol Attenuates Amyloid Peptide Accumulation and Cognitive Deficits in APP/PS1 Mice: The Mediating Role of the Gut–Brain Axis

芝麻酚 认知 早老素 淀粉样蛋白(真菌学) 淀粉样前体蛋白 神经科学 β淀粉样蛋白 化学 内分泌学 内科学 医学 心理学 生物化学 阿尔茨海默病 病理 抗氧化剂 疾病
作者
Qing Liu,Tianzhi Xie,Yujia Xi,Ling Li,Fengfeng Mo,Xuebo Liu,Zhigang Liu,Jin‐Ming Gao,Tian Yuan
出处
期刊:Journal of Agricultural and Food Chemistry [American Chemical Society]
卷期号:69 (43): 12717-12729 被引量:47
标识
DOI:10.1021/acs.jafc.1c04687
摘要

Alzheimer's disease (AD), a neurodegenerative disease, is the leading cause of dementia. Sesamol is a lignan extracted from sesame oil and has been found to exert neuroprotective effects. The present study aimed to investigate the neuroprotective effects of sesamol on APPswe/PS1dE9 transgenic AD mice. The AD mice were fed with a diet supplemented with sesamol (0.075 w/w %). Sesamol treatment improved spatial memory and learning ability in AD mice, improved neuronal damage, and decreased Aβ accumulation. Sesamol protected the synaptic ultrastructure and inhibited neuroinflammatory responses in the brain of AD mice. Sesamol also significantly inhibited the overactivated microglia and reduced the overexpression of TNF-α and IL-1β in the brain of AD mice. Notably, sesamol reshaped gut microbiota by significantly decreasing the relative abundance of Helicobacter hepaticus, Clostridium, and Bacillaceae, enhancing the relative abundance of Rikenellaceae and Bifidobacterium in AD mice. It has been found that sesamol protected the gut barrier integrity and prevented the LPS leakage into the serum. Importantly, sesamol remarkably enhanced the content of SCFAs, including acetate, propionate, isobutyrate, butyrate, and valerate, in AD mice. Correlation analysis indicated that there was a strong correlation between the levels of SCFAs and cognitive functions. These results demonstrated that sesamol attenuated AD-related cognitive dysfunction and neuroinflammatory responses, which could be partly explained by its role in mediating the gut microbe–SCFA–brain axis. Thus, sesamol is a promising nutritional intervention strategy to prevent AD via the microbiota–gut–brain axis.
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