Reduction of colitis-associated colon carcinogenesis by a black lentil water extract through inhibition of inflammatory and immunomodulatory cytokines.

The objective was to compare the impact of black lentil water (BL) and delphinidin 3-O-(2-O-β-d-glucopyranosyl-α-l-arabinopyranoside) (D3G)-rich lentil extracts on tumor development, inflammation, and immune response in an azoxymethane (AOM)/ dextran sodium sulfate (DSS) model. C57BL/6 mice were randomly separated into four groups: healthy control (n=6), AOM/DSS control (n=14), AOM/DSS+BL (600 mg/kg body weight, n=12), and AOM/DSS+D3G (41 mg/kg body weight, equivalent to D3G concentration in BL, n=12). Mice were given treatments for 11 weeks using a voluntary jelly administration. AOM/DSS+BL presented a lower (p<0.05) disease activity index, throughout and at the end (2.4) compared to AOM/DSS (6.3). AOM/DSS+BL mice had an average of 7.8 neoplasms vs. 12.8 for the AOM/DSS (p<0.05). Pro-inflammatory cytokines were downregulated in the colon mucosa: interleukin-1β (-77.5%, -70.7%), interleukin-6 (-44.4%, -44.9%) by AOM/DSS+BL and AOM/DSS+D3G, respectively, compared to AOM/DSS. Interleukin-6 protein expression was decreased by BL in plasma (-72.6%) and gene expression in colon polyps (fold change: -4.0) compared to AOM/DSS. AOM/DSS+D3G non-polyp tissue gene expression clustered with the healthy control tissue with only four genes modified (secreted phosphoprotein 1 and CXC motif chemokine ligands 2, 5, and 10). AOM/DSS+BL downregulated programmed death ligand-1 protein expression in colon tissue (-54.7%) and gene expression by 2.8-fold compared to the AOM/DSS control. In fecal samples, gallic and protocatechuic acids and epicatechin were found, and concentration of most amino acids was lower and unsaturated fatty acids were higher for AOM/DSS+BL and AOM/DSS+D3G. BL and D3G-rich extracts showed anti-inflammatory and pro-immune response effects while BL additionally prevented growth of neoplasia.