Chemoprotective Potential of Cyanidin-3-Glucoside Against 1,2-Dimethylhydrazine-Induced Colorectal Cancer: Modulation of NF-κB and Bcl-2/Bax/Caspase Pathway

Abstract

Colorectal cancer (CRC) represents a significant global health challenge, with approximately 1.8 million new cases diagnosed annually and a mortality toll exceeding 881,000 lives each year. This study aimed to evaluate the chemoprotective efficacy of Cyanidin-3-glucoside (C3G) in a rat model of CRC induced by 1,2-dimethylhydrazine (DMH). Rats were stratified into groups and administered C3G at doses of 10 and 15 mg/kg following DMH exposure to initiate CRC. Key parameters, including organ weights, tumor burdens, and biochemical markers, were meticulously assessed. Administration of C3G significantly restored body weight while reducing the weights of colon and spleen tissues. Moreover, C3G treatment substantially suppressed tumor incidence and weight in DMH-induced CRC rats. Biochemical analysis revealed that C3G markedly reduced levels of CFA, CA19.9, LDH, and nitric oxide (NO). It also modulated lipid profiles, antioxidant activities, and the expression of both Phase I and II enzymes. Inflammatory mediators, including TNF-α, IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, and IL-17, were significantly downregulated. Notably, C3G inhibited inflammatory markers such as COX-2, PGE2, iNOS, and NF-κB while promoting Caspase-3, -6, and -9 activity. Furthermore, it regulated the Bax/Bcl-2 apoptotic axis, reducing the Bcl-2/Bax ratio. Cyanidin-3-glucoside demonstrated potent chemopreventive effects against colorectal cancer in this experimental model. Its mechanism of action is likely mediated through modulation of NF-κB and the Bcl-2/Bax/Caspase pathway, suggesting its potential as a therapeutic agent in CRC management.