PDF(Pubmed)
Abstract：
With the increasing of aging population and the consumption of high-fat diets (HFD), the incidence of Alzheimer\'s disease (AD) has skyrocketed. Natural antioxidants show promising potential in the prevention of AD, as oxidative stress and neuroinflammation are two hallmarks of AD pathogenesis. Here, we showed that quinic acid (QA), a polyphenol derived from millet, significantly decreased HFD-induced brain oxidative stress and neuroinflammation and the levels of Aβ and p-Tau. Examination of gut microbiota suggested the improvement of the composition of gut microbiota in HFD mice after QA treatment. Metabolomic analysis showed significant increase of gut microbial tryptophan metabolites indole-3-acetic acid (IAA) and kynurenic acid (KYNA) by QA. In addition, IAA and KYNA showed negative correlation with pro-inflammatory factors and AD indicators. Further experiments on HFD mice proved that IAA and KYNA could reproduce the effects of QA that suppress brain oxidative stress and inflammation and decrease the levels of of Aβ and p-Tau. Transcriptomics analysis of brain after IAA administration revealed the inhibition of DR3/IKK/NF-κB signaling pathway by IAA. In conclusion, this study demonstrated that QA could counteract HFD-induced brain oxidative stress and neuroinflammation by regulating inflammatory DR3/IKK/NF-κB signaling pathway via gut microbial tryptophan metabolites.
摘要：
随着人口老龄化和高脂饮食(HFD)消费的增加,阿尔茨海默病（AD）的发病率急剧上升。天然抗氧化剂在预防AD方面显示出有希望的潜力，氧化应激和神经炎症是AD发病的两个标志。这里,我们表明奎尼酸(QA)，一种来自小米的多酚，显著降低HFD诱导的脑氧化应激和神经炎症以及Aβ和p-Tau水平。肠道微生物群的检查表明QA处理后HFD小鼠的肠道微生物群的组成改善。代谢组学分析表明，QA导致肠道微生物色氨酸代谢产物吲哚-3-乙酸（IAA）和犬尿烯酸（KYNA）显着增加。此外,IAA和KYNA与促炎因子和AD指标呈负相关。对HFD小鼠的进一步实验证明，IAA和KYNA可以重现QA的作用，从而抑制脑氧化应激和炎症，并降低Aβ和p-Tau的水平。IAA给药后大脑的转录组学分析显示IAA对DR3/IKK/NF-κB信号通路的抑制作用。总之,这项研究表明，QA可以通过肠道微生物色氨酸代谢产物调节炎性DR3/IKK/NF-κB信号通路来对抗HFD诱导的脑氧化应激和神经炎症。
