1.The mechanism of isoliquiritigenin on ameliorating non-alcoholic fatty liver disease in mice by regulating gut microbiota and repairing gut barrier function
Haiyan ZENG ; Lina JIAN ; Huixing WU ; Benjie ZHOU ; Shijian XIANG
China Pharmacy 2023;34(23):2848-2854
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.
2.Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis
Huixing WU ; Zhenhua ZHANG ; Changrui LONG ; Guifen GUO ; Yanyu WANG ; Yanchun CHEN ; Juxiong FU ; Shijian XIANG ; Benjie ZHOU ; Chengyu LU
China Pharmacy 2024;35(13):1570-1575
OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group (0.5% carboxymethyl cellulose sodium solution), model group (0.5% carboxymethyl cellulose sodium solution), and BP low-dose and high-dose groups (50, 100 mg/kg), with 10 mice in each group. Except for the normal control group, the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model; they were given relevant medicine/solution intragastrically, once a day, for consecutive 8 weeks. After the last medication, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver pathological changes were observed; the expressions of α-smooth muscle actin (α-SMA) and Collagen Ⅰ were detected in liver tissue; the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group, serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups (P<0.05), while liver fibrosis was improved significantly. Meanwhile, metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group, of which 18 substances were upregulated and 157 substances were downregulated; the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism, butanoate metabolism, fatty acid synthesis, tyrosine metabolism, β-alanine metabolism, nicotinic acid and nicotinamide metabolism, glutathione metabolism, etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism, butanoate metabolism, glutathione metabolism and so on in rats with liver fibrosis.