Background: Baicalein is an active ingredient extracted from the root of S. baicalensis Georgi, which exhibits cardiovascular protection, anti-inflammatory, and anti-microbial properties. Our previous study showed that chronic treatment of Baicalein ameliorated cognitive dysfunction in a mouse model of Alzheimer's disease (AD). However, it remains unknown whether Baicalein ameliorates cognitive deficits in AD mouse models by altering gut microbiota and its metabolites.Methods: Behavioral tests, metagenomic and untargeted metabolomics analyses were used to evaluate the effects of Baicalein on the APP/PS1 mice.Results: Our research showed that treatment of Baicalein for 2 weeks ameliorated cognition and memory in a dose-dependent manner, as indicated by the significant increases in the Discrimination index and Number of crossings and decrease in latency to the previous platform location in 8-month of age APP/PS1 mice in novel object recognition and water maze tests. The metagenomic analysis showed the abundance of the dominant phyla in all groups, including Bacteroidetes (14.59%–67.02%) and Firmicutes (20.19%–61.39%). LEfSe analysis of metagenomics identified three species such as s__Roseburia_sp_1XD42_69, s__Muribaculaceae_bacterium_Isolate_104_HZI, s__Muribaculaceae_bacterium_Isolate_110_HZI as Baicalein-treated potential biomarkers. Metabolite analysis revealed the increment of metabolites, including glutamate, thymine and hexanoyl-CoA.Conclusion: The effects of Baicalein on memory and cognition may relate to the metabolism of nucleotides, lipids and glucose.

中文翻译：

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黄芩素校正的肠道微生物群可能是改善 APP/PS1 小鼠记忆和认知缺陷的基础

背景：黄芩素是从黄芩根中提取的一种活性成分，具有保护心血管、抗炎和抗菌的特性。我们之前的研究表明，黄芩素的长期治疗可改善阿尔茨海默病 (AD) 小鼠模型的认知功能障碍。然而，尚不清楚黄芩素是否通过改变肠道微生物群及其代谢物来改善 AD 小鼠模型的认知缺陷。方法：行为测试、宏基因组学和非靶向代谢组学分析用于评估黄芩素对 APP/PS1 小鼠的影响。结果：我们的研究表明，黄芩素治疗 2 周以剂量依赖的方式改善认知和记忆，正如在新物体识别和水迷宫测试中 8 个月大的 APP/PS1 小鼠的辨别指数和交叉次数的显着增加以及到先前平台位置的延迟减少所表明的那样。宏基因组分析显示所有类群中优势门的丰度，包括拟杆菌门 (14.59%–67.02%) 和厚壁菌门 (20.19%–61.39%)。宏基因组学的 LEfSe 分析确定了三个物种，如 s__Roseburia_sp_1XD42_69、s__Muribaculaceae_bacterium_Isolate_104_HZI、s__Muribaculaceae_bacterium_Isolate_110_HZI 作为黄芩素处理的潜在生物标志物。代谢物分析显示代谢物增加，包括谷氨酸、胸腺嘧啶和己酰辅酶A。结论：黄芩素对记忆和认知的影响可能与核苷酸、脂质和葡萄糖的代谢有关。