Abstract: This investigation is designed to delineate the antineoplastic properties of ursolic acid against colorectal cancer and to elucidate underlying molecular mechanisms, including its influence on gut microbiota homeostasis as assessed by alpha/beta diversity and functional profiling. The study initially treated HCT116 and SW480 colorectal cancer cell lines with ursolic acid at concentrations ranging from 0 to 90 Formula: see textM to evaluate its impact on cell proliferation. Building on this, the researchers re-exposed the colorectal cancer cells to ursolic acid at 5 Formula: see textM, 10 Formula: see textM, and 20 Formula: see textM for 24Formula: see texth to comprehensively assess its effects on key cellular processes such as migration, colony formation, apoptosis, and cell cycle regulation. Additionally, the same concentrations (5 Formula: see textM, 10 Formula: see textM, and 20 Formula: see textM) were used to re-expose the cells for 24Formula: see texth to evaluate the modulation of the Wnt/Formula: see text-catenin signaling pathway by ursolic acid. In the in vivo 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/Formula: see text-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/Formula: see text-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/Formula: see text-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/Formula: see text-catenin signaling, and exercising additional effects on gut microbiota modulation.
Zhao et al. (Sat,) studied this question.