Moringa oleifera leaves alleviated inflammation through downregulation of IL-2, IL-6, and TNF-α in a colitis-associated colorectal cancer model

New chemopreventive alternatives are needed due to the rising worldwide incidence of colorectal cancer. The objective was to evaluate the chemopreventive activity of Moringa oleifera leaves (MO) in a colitis-associated colon carcinogenesis model. We hypothesized that MO contain bioactive compounds capable of modulating the expression of genes involved in the inflammatory response and carcinogenesis. Forty-eight male mice (CD-1) were divided into six groups; 1: Healthy control; 2: Positive control induced with azoxymethane (AOM, 10 mg/Kg body weight, intraperitoneal injection) and three cycles of dextran sodium sulfate (DSS, 1.5% in drinking water); groups 3, 4, and 5 were induced with AOM/DSS and supplemented with 5%, 10%, and 20% of MO, respectively; group 6: had no disease induction and supplemented with 20% of MO. Mice were treated for 12 weeks and euthanized. Significant differences (p < 0.05) were found for the moringa-administered groups in morphological and histopathological parameters compared to the AOM/DSS control. A decrease in myeloperoxidase activity (~50%) and lipid peroxidation (1.9–3.1 times) were found in groups with 10% and 20% of MO compared to the AOM/DSS control (p < 0.05). The group supplemented with 10% MO showed a significant increase (~3 times) in butyrate and propionate in fecal and cecal content. Groups supplemented with 10%, and 20% MO showed a reduction in proinflammatory cytokines in serum (MCP-1, IL-6, TNF-α) compared to the AOM/DSS control. Treatment with 10% MO induced differential expression of 65 genes in colon tissue such as IL-2, IL-6, TNF, IL-1ß, and INF-γ. MO downregulated proinflammatory mediators showing chemopreventive properties against inflammatory response and colon carcinogenesis.