AUTHOR=Li Zhiyue , Zeng Qiang , Hu Shengquan , Liu Zhanyan , Wang Shuting , Jin Yu , Li Limin , Ou Hanlin , Wu Zhengzhi 

TITLE=Chaihu Shugan San ameliorated cognitive deficits through regulating gut microbiota in senescence-accelerated mouse prone 8

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1181226

DOI=10.3389/fphar.2023.1181226

ISSN=1663-9812

ABSTRACT=Traditional Chinese medicines exhibit promising preventive effects on Alzheimer’s disease (AD). Chaihu Shugan San (CSS) is a well-known traditional herbal formula in which several kinds of ingredients have potential on ameliorating AD. The present study aimed to evaluate the effects of Chaihu Shugan San (CSS) on the microbiota-gut-brain axis and cognitive deficits of senescence-accelerated mouse prone 8 (SAMP8) mice, as well as investigate the underlying mechanisms. Thirty 5-month-old SAMP8 mice were randomly divided into model group (SAMP8), CSS low dose treatment group (CSSL) and CSS high dose treatment group (CSSH), while ten SAMR1 mice were used as normal control and ten SAMP8 mice treated with donepezil were used as positive control of cognitive function. CSS was orally administrated to 5-month-old SAMP8 mice for eight weeks. Morris water maze test was used to evaluate cognitive function. Histological staining was used to observe neuronal injury and Aβ deposition. Transmission electron microscopy was used to observe the synaptic ultrastructure. 16S rRNA gene analysis was perfomed to measure the changes of intestinal microbiota. The results showed that CSS significantly improved the learning function and memory deficits of aged SAMP8 mice in Morris water maze examination. CSS ameliorated neuronal injury, synaptic injuries and Aβ deposition in the brain of SAMP8 mice. In addition, CSS also significantly improved microbiota composition in terms of elevating Lactobacillus reuteri, in company with decreasing Staphylococcus xylosus in the feces of aged SAMP8 mice. These findings suggested that CSS might have a preventive potential for cognitive deficits in aging through regulating gut microbiotatargeting the microbiota-gut-brain axis, which paved the way to the application of CSS on prevention and therapeutic for mild cognitive impairment as well as Alzheimer’s disease.