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

Authors: MAZEWSKI, CANDICE - University Of Illinois; LUNA, DIEGO - University Of Illinois; Berhow, Mark; GONZALEZ DE MEJIA, ELVIRA - University Of Illinois

Submitted to: Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/28/2020
Publication Date: 1/31/2020
Citation: Mazewski, C., Luna-Vital, D., Berhow, M., Gonzalez de Mejia, E. 2020. Reduction of colitis-associated colon carcinogenesis by a black lentil water extract through inhibition of inflammatory and immunomodulatory cytokines. Carcinogenesis. 41(6):790-803. https://doi.org/10.1093/carcin/bgaa008.
DOI: https://doi.org/10.1093/carcin/bgaa008

Interpretive Summary: Black lentils are enriched in polyphenolic compounds, such as anthocyanins, which have been shown to have anti-inflammatory and anti-cancer effects. Therefore, extracts prepared from black lentils using water were evaluated for their effects on tumor development, inflammation and immune response in a mouse model system for colon cancer. Mice were fed black lentil extracts and after exposure to a cancer-inducing carcinogen, were evaluated for a variety of end markers determining their effects on the development of inflammation, which can lead to the development of a variety chronic diseases. These extracts demonstrated both anti-inflammatory and pro-immune response effects in the mouse model and some additionally prevented growth of neoplasia—abnormal tissue growth that may lead to tumors. This study, to our knowledge, is the first to demonstrate the ability of antioxidant-rich black lentil extracts to modulate communication between immune cells and induce anti-inflammatory and anti-carcinogenic effects.

Technical Abstract: The objective was to compare the impact of black lentil water (BL) and delphinidin 3-O-(2-O-ß-d-glucopyranosyl-a-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-1ß (-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.