title: Cocoa polyphenols prevent inflammation in the colon of azoxymethane-treated rats and in TNF-α-stimulated Caco-2 cells.
abstract: Numerous lines of evidence support a relationship between intestinal inflammation and cancer. Therefore, much attention has recently been focused on the identification of natural compounds with anti-inflammatory activities as a strategy to suppress the early stages of colorectal cancer. Because cocoa is a rich source of bioactive compounds, the present study investigated its anti-inflammatory properties in a rat model of azoxymethane (AOM)-induced colon carcinogenesis and in TNF-α-stimulated Caco-2 cells. A total of forty male rats were fed with control or cocoa-enriched diets (12 %) during 8 weeks and injected with saline or AOM (20 mg/kg body weight) during the third and fourth week (n 10 rats/group). At the end of the experiment, colon samples were evaluated for markers of inflammation. The anti-inflammatory activity of a cocoa polyphenolic extract (10 μg/ml) was examined in TNF-α-stimulated Caco-2 cells, an in vitro model of experimentally induced intestinal inflammation. The signalling pathways involved, including NF-κB and the mitogen-activated protein kinase family such as c-Jun NH₂-terminal kinases (JNK), extracellular signal-regulated kinases and p38, were also evaluated. The results show that the cocoa-rich diet decreases the nuclear levels of NF-κB and the expression of pro-inflammatory enzymes such as cyclo-oxygenase-2 and inducible NO synthase induced by AOM in the colon. Additionally, the experiments in Caco-2 cells confirm that cocoa polyphenols effectively down-regulate the levels of inflammatory markers induced by TNF-α by inhibiting NF-κB translocation and JNK phosphorylation. We conclude that cocoa polyphenols suppress inflammation-related colon carcinogenesis and could be promising in the dietary prevention of intestinal inflammation and related cancer development.
authors.affiliation: Departamento de Metabolismo y Nutrición, Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN-CSIC), José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain.
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Rodríguez-Ramiro
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramos
authors.forename: Elvira
authors.initials: E
authors.lastname: López-Oliva
authors.forename: Angel
authors.initials: A
authors.lastname: Agis-Torres
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
authors.forename: Luis
authors.initials: L
authors.lastname: Goya
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Martín
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001397:Azoxymethane; D015415:Biomarkers / Q000378:metabolism; D002099:Cacao / Q000737:chemistry*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004032:Diet; D015536:Down-Regulation; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D016328:NF-kappa B; D010936:Plant Extracts; D059808:Polyphenols; D014409:Tumor Necrosis Factor-alpha; D048670:MAP Kinase Kinase 4; D001397:Azoxymethane