Investigating the Role and Underlying Mechanisms of 18β-Glycyrrhetinic Acid in the Therapy of Ulcerative Colitis Through Modulation of the PPAR-γ/NF-κB Signaling Pathway.

BACKGROUND

18β-glycyrrhetinic acid (18β-GA), a triterpenoid saponin naturally occurring in , has potent anti-inflammatory and antioxidant properties, but the therapeutic efficacy and precise mechanism of 18β-GA in ulcerative colitis (UC) remain unclear.

METHODS

To determine the therapeutic potential of 18β-GA, we constructed a dextran sodium sulfate (DSS)-induced UC model on a cohort of thirty-two female BALB/c mice and used mouse peritoneal macrophages to establish a co-culture system for in vitro experiments. We measured body weight, fecal characteristics, colon length, disease activity index (DAI) of mice, and the degree of colonic histological lesions. Changes in the composition of intestinal flora were monitored using high-throughput 16S rDNA sequencing. Combining network pharmacology and molecular docking to predict pharmacological mechanisms and using Western blot for validation.

RESULTS

18β-GA significantly alleviated DSS-induced weight loss, colon length reduction, an increase in the DAI score, and pathological colon damage. Additionally, 18β-GA promotes a favorable environment that hindered the proliferation of pathogenic bacteria, thereby promoting gut health. Co-culture and scratch assays confirmed that 18β-GA promotes mucosal repair. Network pharmacology and molecular docking predicted potential drug targets, while Western blot analysis revealed that 18β-GA downregulated phosphorylated nuclear factor kappa-B (p-NF-κB) and activated the peroxisome proliferator-activated receptor γ (PPAR-γ).

CONCLUSION

The therapeutic application of 18β-GA in UC demonstrates a multifaceted pharmacological process. It fosters harmonious intestinal microbiota, reinstates the integrity of the intestinal barrier, and exerts its beneficial effects through modulating the PPAR-γ/NF-κB signaling pathway, underscoring its potential as a therapeutic agent for UC.