Effect of Liquiritigenin on Intestinal Flora in Ovariectomized APP/PS1 Transgenic Mice / 中山大学学报(医学科学版)

ABSTRACT

ObjectiveTo investigate the effect of liquiritigenin （LG） on intestinal flora in menopausal APP/PS1 mice. MethodsA total of forty 3-month-old female APP/PS1 mice were randomly divided into sham surgery group （n=20） and ovariectomy group （n=20）. Seven days after surgery， the ovariectomy group was randomly divided into ovariectomy control group （OVX， n=10）， ovariectomy + liquiritigenin treatment group （OVX + LG， n=10）， and the sham surgery group was randomly divided into liquiritigenin treatment group （LG， n=10） and reagent control group （Sham， n=10）， and ten C57BL/6J mice were taken as WT group. The dose of LG group and OVX + LG group was 30 mg•kg-1•d-1. After 90 days of drug treatment， fecal samples were gathered， genomes were extracted， and intestinal flora were analyzed by 16S rDNA Amplicon Sequencing. Morris water maze was performed to evaluate learning and memory abilities of mice. Immunofluorescence was used to observe the deposition of senile plaques （SP） in the brain of mice. ResultsThe results of water maze showed that LG significantly improved the learning memory ability of APP/PS1 mice with/without OVX （P<0.05）， and reduced the number of SPs in the brain of APP/PS1 mice with/without OVX， and the differences were statistically significant （P<0.000 1）. 16s rDNA sequencing analysis of the relative abundance of gut microbiota proved that LG treatment significantly increased the relative abundance of Firmicutes and Lactobacillus （P<0.05） and reduced the relative abundance of harmful bacteria belong to Bacteroidetes （P<0.05） in APP/PS1 mice intestines with/without menopause. After LG treatment， the relative abundance of Allobaculun elevated in the intestines of APP/PS1 mice， while declined in the intestines of menopausal APP/PS1 mice， but the difference was not statistically significant. LEfSe analysis revealed the bacteria with the most differential abundance of the gut microbiota of WT mice were Firmicutes， Bacillus， and Lactobacillales （P<0.05）； Lactobacillus reuteri had a greater influence on the LG group （P<0.05）； Bacteroidia， Bacteroidales and Bacteroides gathered in the intestines of mice in the Sham group （P<0.05）. Firmicutes and Allobaculum were the dominant in the WT group （P<0.05）； Bacteroides， Bacteroidia and Bacteroidales were more abundant in the Sham group（P<0.05）； Bacterroidaceae and Bacteroides had the most differential abundances in the OVX group （P<0.05）； Lactobacillaceae and Lactobacillus were more abundant in the intestines in the OVX + LG group （P<0.05）. ConclusionLG could improve the ratio of beneficial and harmful bacteria in the intestines of APP/PS1 mice before and after menopause. Liquiritigenin treatment showed consistent variations in intestinal flora in APP/PS1 mice with or without ovariectomy. It is presumed that menopausal APP/PS1 mice have lipid metabolism disorders which requires further study.