AUTHOR=Shi Jing , Chen Jie , Xie Xinyun , Li Yuanyuan , Ye Wenjing , Yao Jianbiao , Zhang Xiangnan , Zhang Tianyuan , Gao Jianqing TITLE=Baicalein-corrected gut microbiota may underlie the amelioration of memory and cognitive deficits in APP/PS1 mice JOURNAL=Frontiers in Pharmacology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1132857 DOI=10.3389/fphar.2023.1132857 ISSN=1663-9812 ABSTRACT=

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.