Therapeutic Prospects of Ursolic Acid in Colorectal Cancer: Modulation of the Wnt/β-Catenin Signaling Pathway and Gut Microbiota Composition

experiments, based on previously published literature, researchers administered ursolic acid at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg to a CRC mouse model induced by azoxymethane/dextran sulfate sodium (AOM/DSS). Subsequently, the effects of ursolic acid were evaluated through multiple parameters, which included body weight, survival rate, colorectal length, inflammatory markers, pathological changes, apoptosis, cell cycle phase distribution, Wnt/β-catenin signaling pathway activity, and gut microbiota composition analyzed via 16S rRNA sequencing targeting the V3-V4 hypervariable regions. The results demonstrated that ursolic acid potently represses the proliferative, migratory, and clonogenic capabilities of HCT116 and SW480 while concomitantly inducing apoptosis and cell cycle arrest. The antineoplastic actions of ursolic acid are attributed to its inhibitory effect on Wnt/β-catenin signaling. In the azoxymethane/dextran sodium sulfate-induced colorectal cancer model, the administration of ursolic acid yields marked enhancements in terms of body weight maintenance, survival metrics, attenuation of inflammatory responses, reduction of histopathological lesions, potentiation of apoptosis, disruption of the cell cycle, suppression of the Wnt/β-catenin pathway, and remodeling of both the gut microbiota composition and its associated metabolic activities. Ursolic acid, a phytochemical prevalent in traditional medicinal plants, demonstrates potent anti-CRC activity by inducing apoptosis, inducing cell cycle arrest, inhibiting Wnt/β-catenin signaling, and exercising additional effects on gut microbiota modulation.