Neohesperidin protects against colitis-associated colorectal cancer in mice via suppression of the NF-κB/p65 and MAPK pathways.

Patients with inflammatory bowel disease (IBD) are at increased risk of developing colitis-associated colorectal cancer (CAC). Neohesperidin (NHP), a flavanone glycoside derived from citrus fruits, has been reported to have anti-inflammatory, antioxidant, and anticancer potential. However, the function of NHP on tumorigenesis has not been well understood. To investigate the potential chemopreventive effects of NHP on CAC development, an in vivo azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was used and NHP was administered by daily gavage for 10 weeks throughout the model period. In this study, we found that NHP effectively ameliorated AOM/DSS-induced pathological symptoms of colitis and thus inhibited colon tumorigenesis in mice. NHP treatment attenuated tumor proliferation, induced apoptosis, and inhibited angiogenesis during CAC development. In addition, NHP inhibited macrophage infiltration and reduced the expression of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and COX-2 at both mRNA and protein levels, and the higher the concentration of NHP, the better the inhibition. It is worth noting that the positive therapeutic agent mesalazine (100 mg/kg) had a therapeutic effect comparable to that of a low concentration of NHP (50 mg/kg), but less effective than the same concentration of NHP (100 mg/kg). In addition, NHP may exert anti-inflammatory and anticancer effects by inhibiting the NF-κB/p65 and ERK/p38 MAPK pathways. Our findings highlight the potential of NHP as a potential therapeutic candidate for IBD and CAC.