Protective Effects of Licochalcone A Against Alcoholic Liver Injury in Mice by Modulating the Gut–Liver Axis and TLR4/NF-κB Pathway

This study intended to elucidate the preventive effects of Licochalcone A (Lico A, a flavonoid from Glycyrrhiza inflata) on acute alcoholic liver injury (AALI) in mice and its mechanisms. Lico A (50, 100 mg/kg) markedly decreased the serum ALT, AST, and ALP levels (p < 0.05) and elevated the ALB and TP levels in AALI mice (p < 0.05). Lico A (100 mg/kg) markedly reduced the hepatic levels of MDA, NO, TNF-α, IL-1β, and IL-6 in AALI mice (p < 0.05), while elevating SOD, GSH, ADH, and ALDH activities (p < 0.05). Furthermore, Lico A (100 mg/kg) downregulated TLR4, MyD88, IKKβ, p-IκBα/IκBα, and p-NF-κB p65/NF-κB p65 levels in the liver tissue of AALI mice (p < 0.05) and diminished the serum LPS and DAO contents (p < 0.05). Lico A (50, 100 mg/kg) upregulated the expression of the intestinal tissue ZO-1 and Occludin in AALI mice. Pathological observation also showed that Lico A significantly improved the liver tissue and intestinal mucosa tissue damage caused by alcohol. Additionally, Lico A altered gut microbiota composition, accompanied by increased concentrations of fecal short-chain fatty acids (SCFAs), which restored microbial diversity and elevated the relative abundance of Actinomycetota, Bacteroidota, Bacillota_A_368345, Limosilactobacillus, Lactobacillus, and Bifidobacterium_388775. These results indicated that Lico A had better hepatoprotective effects on AALI, and its mechanisms may involve modulation of the gut–liver axis and the TLR4/NF-κB signaling pathway.