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α-糖基异槲皮苷通过改变小鼠肠道微生物群-血脑轴对记忆的潜在影响

Potential Effects of Alpha-Glycosyl Isoquercitrin on Memory by Altering the Gut Microbiota-Blood-Brain Axis in Mice.

作者信息

Liu Hong, Inoue Ryo, Koyanagi Mihoko, Hayashi Shim-Mo, Nagaoka Kentaro

机构信息

Laboratory of Veterinary Physiology, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.

Laboratory of Animal Science, Department of Applied Biological Sciences, Setsunan University, Osaka 573-0101, Japan.

出版信息

J Agric Food Chem. 2023 Nov 1;71(43):15991-16002. doi: 10.1021/acs.jafc.3c00897. Epub 2023 Oct 20.

DOI:10.1021/acs.jafc.3c00897
PMID:37861708
Abstract

Alpha-glycosyl isoquercitrin (AGIQ), composed of isoquercitrin and glycosylated quercetin, has multiple biological effects. Here, we further examined the influence of AGIQ on brain function and provided its potential mechanism. Male C57BL/6 mice were treated with 0, 0.005, and 0.05% AGIQ in drinking water for 4 weeks prior to behavioral testing. Behavior tests showed that 0.05% AGIQ treatment significantly improved learning and memory function without affecting emotion. In the hippocampus, the gene expression of antioxidative defense enzymes was upregulated after 0.05% AGIQ treatment. In contrast, AGIQ caused significant alterations in the microbial abundance of genera , , and associated with memory function. Metabolomics analysis identified that taurine concentration was significantly increased in serum and hippocampus from AGIQ-treated mice. The correlation analysis suggested that elevated serum taurine levels were closely related to the abundance of , indicating the underlying crosstalk of gut microbiota and serum metabolites. In vitro fecal culture further demonstrated that AGIQ could increase the level of . Taurine could exert antioxidant activity in SH-SY5Y neuroblastoma cell lines in vitro. Finally, vancomycin-induced alterations of gut microbiota attenuated the taurine increases in the serum and the antioxidant gene level in the hippocampus by AGIQ. Taken together, it is likely that AGIQ could increase genus abundance and ultimately increase taurine levels in serum and hippocampus to improve learning and memory function, relying on the gut microbiota-blood-brain axis. Our results supply a new view for understanding effects of AGIQ on brain function.

摘要

α-糖基异槲皮苷(AGIQ)由异槲皮苷和糖基化槲皮素组成,具有多种生物学效应。在此,我们进一步研究了AGIQ对脑功能的影响并提供了其潜在机制。在行为测试前4周,用0%、0.005%和0.05%的AGIQ处理雄性C57BL/6小鼠饮用水。行为测试表明,0.05%的AGIQ处理显著改善了学习和记忆功能,而不影响情绪。在海马体中,0.05%的AGIQ处理后抗氧化防御酶的基因表达上调。相比之下,AGIQ导致与记忆功能相关的属、和的微生物丰度发生显著变化。代谢组学分析确定,AGIQ处理小鼠的血清和海马体中牛磺酸浓度显著增加。相关性分析表明,血清牛磺酸水平升高与的丰度密切相关,表明肠道微生物群与血清代谢物之间存在潜在的相互作用。体外粪便培养进一步证明AGIQ可以提高的水平。牛磺酸在体外SH-SY5Y神经母细胞瘤细胞系中可发挥抗氧化活性。最后,万古霉素诱导的肠道微生物群改变减弱了AGIQ引起的血清中牛磺酸的增加和海马体中抗氧化基因水平的升高。综上所述,AGIQ可能通过肠道微生物群-血-脑轴增加属的丰度,并最终提高血清和海马体中牛磺酸水平,从而改善学习和记忆功能。我们的结果为理解AGIQ对脑功能的影响提供了新的视角。

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