Licorice Flavonoid Extract Ameliorates Intestine Damage in Ulcerative Colitis via MAPK/NF-κB Signaling Modulation and Gut Microbiome Remodeling

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology, characterized by non-specific colonic inflammation. Licorice (<i>Glycyrrhiza uralensis</i> Fisch.), a food-medicine dual-use botanical, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties, suggesting therapeutic potential for UC. However, the specific bioactive components of licorice and their underlying mechanisms of action require further elucidation. In this study, we investigated the efficacy and mechanisms of licorice flavonoid extract (LF) in a dextran sulfate sodium (DSS)-induced murine model of UC. The results demonstrated that oral administration of LF significantly alleviated disease pathology indices, reduced colon shortening, and improved histopathological colon damage. LF treatment suppressed the production of pro-inflammatory cytokines, likely through inhibiting the phosphorylation of MAPK and NF-κB p65, while upregulating PPARγ expression. Additionally, LF intervention restored gut microbial diversity, increasing the abundance of beneficial taxa such as Bacteroidetes and Firmicutes. The chemical characterization of LF revealed that 15 flavonoid compounds contribute to its therapeutic basis. These findings demonstrate that LF mitigates UC via integrated anti-inflammatory, immunomodulatory, and microbiota-regulating mechanisms, highlighting its potential as a natural therapeutic agent for UC management.