Objective To study the protective effect and mechanism of taraxasterol on alcoholic liver disease (ALD) from the perspective of gut microbiota and liver metabolites. Methods C57BL/6J mice were randomly divided into control group, model group, silibinin (100 mg/kg) group, taraxasterol high- and low-dose (10, 5 mg/kg) groups, with eight mice in each group. After continuous administration for four weeks and daily administration for 4 h, the ALD model was induced in mice by ig 53° red star erguotou. Liver function, liver tissue oxidative stress and inflammation related indicators in serum were detected. Hematoxylin-eosin (HE) staining was used to observe pathological changes in liver tissue. Western blotting was used to detect the expressions of zonula occludin-1 (ZO-1) and Occludin proteins in small intestine tissue. Metabolomics and 16S rRNA sequencing were used to detect changes in liver metabolites and gut microbiota. Results Compared with model group, taraxasterol significantly reduced the liver index and levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG) in serum of ALD mice (P < 0.05, 0.01), increased the activity of superoxide dismutase (SOD) in liver tissue (P < 0.05, 0.01), reduced the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver tissue (P < 0.05, 0.01), improved liver pathological changes, and upregulated the expressions of ZO-1 and Occludin in small intestine tissue (P < 0.05, 0.01). 16S rRNA sequencing analysis showed that taraxasterol effectively regulated the diversity of gut microbiota in ALD mice, improved the disorder of gut microbiota structure, and increased the abundance of beneficial bacteria such as Bacteroides, Bifidobacterium and Parabacteroides, decreased the abundance of pathogenic bacteria such as Escherichia Schilla and Streptococcus. Metabolomics analysis showed that taraxasterol reversed alcohol induced liver metabolic disorders, particularly in the sphingolipid and linoleic acid metabolic pathways, and increased levels of acetic acid, butyric acid and valeric acid. Conclusion Taraxasterol alleviates liver inflammation and alleviates ALD by regulating changes in gut microbiota and metabolites.

taraxasterol  /  alcoholic liver disease  /  metabolite  /  gut microbiota  /  oxidative stress  /  inflammatory response