The mechanism of isoliquiritigenin on ameliorating non-alcoholic fatty liver disease in mice by regulating gut microbiota and repairing gut barrier function
- VernacularTitle:异甘草素调控肠道菌群和肠屏障功能改善小鼠非酒精性脂肪性肝病的作用机制
- Author:
Haiyan ZENG
1
;
Lina JIAN
2
;
Huixing WU
2
;
Benjie ZHOU
3
,
4
;
Shijian XIANG
3
Author Information
1. Dept. of Clinical Laboratory,Shenzhen (Guangming) Hospital of University of Chinese Academy of Sciences,Guangdong Shenzhen 518106,China
2. School of Pharmacy,Guangdong Medical University,Guangdong Dongguan 523808,China
3. Dept. of Pharmacy,the Seventh Affiliated Hospital of Sun Yat-sen University,Guangdong Shenzhen 518107,China
4. Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research,Guangdong Shenzhen 518107,China
- Publication Type:Journal Article
- Keywords:
isoliquiritigenin;
gut microbiota;
gut mucosal barrier;
non-alcoholic fatty liver disease
- From:
China Pharmacy
2023;34(23):2848-2854
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the effects of isoliquiritigenin (ISL) regulating gut microbiota and repairing gut barrier function in model mice with non-alcoholic fatty liver disease (NAFLD), and to clarify its mechanism for improving NAFLD. METHODS Thirty male C57BL/6J mice were randomly divided into the normal (ultrapure water), model group (ultrapure water), ISL group (100 mg/kg), with 10 mice in each group. Model group and ISL group were fed with high-fat diet for 19 weeks to establish NAFLD model; at the same time, the mice were given relevant medicine/ultrapure water intragastrically. The changes of body weight in mice were recorded, and liver index, white fat index and brown fat index were calculated. The pathological changes of liver tissue and colon tissue as well as lipid accumulation were observed in mice. The levels of total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) E-mail:xiangshj3@mail.sysu.edu.cn in serum or liver were measured; the serum levels of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) and the levels of IL-6, IL-1β and TNF-α mRNA expression in liver tissue were detected. Fecal samples underwent 16S rDNA sequencing analysis, and the effects of ISL on gut microbiota structure of mice were investigated. The expressions of gut mucosal barrier-related proteins (Claudin-4, Occludin and ZO-1) were determined in the colon tissue of mice. RESULTS Compared with model group, the body weight, liver index, the levels of TC in liver tissue and serum, the levels of AST and ALT in serum, the levels of IL-6, IL-1β and TNF-α in serum, and the mRNA expression of TNF-α in liver tissue were all decreased significantly in ISL group, while brown fat index was increased significantly. The inflammation and damage of liver tissue were significantly improved, and the NAFLD activity score and the proportion of lipid staining area were significantly reduced (P<0.05). ISL could significantly up-regulate the relative abundance of beneficial microbiota (norank_f_Muribaculaceae, Odoribacter, Ruminiclostridium, etc.) and the expressions of intestinal barrier function- related proteins, but could significantly down-regulate the relative abundance of harmful bacteria (Desulfovibrio, norank_f_Lachnospiraceae, unclassified_p_Firmicutes), and could repair intestinal barrier. CONCLUSIONS ISL could significantly delay the progress of NAFLD, the mechanism of which may be associated with regulating gut microbiota and improving gut barrier function.