Cocoa polyphenols prevent inflammation in the colon of azoxymethane-treated rats and in TNF-α-stimulated Caco-2 cells

Ildefonso Rodriguez Ramiro, Sonia Ramos, Elvira López-Oliva, Angel Agis-Torres, Laura Bravo, Luis Goya, Maria Angeles Martín

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67 Citations (Scopus)


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-a-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-a-stimulated Caco-2 cells, an in vitro model of experimentally induced intestinal inflammation. The signalling pathways involved, including NF-?B 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-?B 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-a by inhibiting NF-?B 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.
Original languageEnglish
Pages (from-to)206-215
Number of pages10
JournalBritish Journal of Nutrition
Issue number2
Publication statusPublished - 28 Jul 2013


  • Anti-Inflammatory Agents
  • Phytotherapy
  • NF-kappa B
  • Animals
  • Tumor Necrosis Factor-alpha
  • Polyphenols
  • Cacao
  • Plant Extracts
  • Humans
  • Inflammation
  • Rats
  • Neoplasms
  • Phosphorylation
  • Colon
  • Down-Regulation
  • MAP Kinase Kinase 4
  • Azoxymethane
  • Inflammation Mediators
  • Diet
  • Signal Transduction
  • Biological Markers
  • Male

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