Abstract

This study evaluates the therapeutic efficacy and safety of Vernonia Amygdalina extract (VAEE) in treating colorectal cancer (CRC) induced by azoxymethane/dextran sulfate sodium (AOM/DSS) in mice and to elucidate the underlying mechanisms. The study utilized a mouse model of CRC to assess the impact of VAEE on pathological markers, inflammatory mediators, and oxidative stress. Phytochemical profiling of VAEE was conducted using LC-HRMS, focusing on phenolic compounds. The extract's antioxidant activity was quantified, and its safety profile was verified through acute toxicity assessments. VAEE significantly mitigated the AOM/DSS-induced reduction in colon length and weight loss in a dose-dependent manner. The treatment decreased pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) while increasing the anti-inflammatory cytokine IL-10. VAEE also demonstrated strong antioxidant activity and did not adversely affect blood, kidney, or liver biomarkers, confirming its non-toxicity. Protein-protein interaction analysis suggested VAEE's role in inhibiting inflammatory markers, including COX-2, IL-18, and NF-kB. Molecular docking results supported the extract's affinity for these proteins, indicating potential as a COX-2 inhibitor. VAEE exhibits potent anti-inflammatory, antioxidative, and anticarcinogenic properties against CRC, with a favorable safety profile. These findings advocate for the integration of VAEE as a novel therapeutic agent in CRC treatment. Further investigations into its molecular mechanisms and long-term effects are warranted to facilitate clinical translation.

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