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-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 mg/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-kB and the mitogen-activated protein kinase family such as c-Jun NH 2 -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-kB 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-kB 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.

Diet-related inflammation and oesophageal cancer by histological type: a nationwide case–control study in Sweden

“…In contrast, accumulating evidence has shown that some food types are protective against cancer, including oesophageal cancer, through their anti-inflammatory effects; e.g. soy protein inhibits inflammation by inhibiting the NF-κB and AKT signalling pathway [45], cocoa polyphenols prevent inflammation in the colon [46], olive oil and omega-3 fatty acids possess anti-inflammatory effects [47]. Increased risk by BMI may reflect the potential modulation of inflammation between diet, body composition, and oesophageal cancer.…”

The urinary phenolic acid profile varies between younger and older adults after a polyphenol-rich meal despite limited differences in in vitro colonic catabolism

“…With their simpler structure and increased bioavailability, phenolic acids are one of the major (poly)phenol metabolites present in blood with a maximum plasma concentration of 0-4 µmol/L with an intake of 50 mg aglycone equivalents [62], and reported anti-inflammatory, anti-carcinogenic, anti-proliferative, anti-glycative and prebiotic properties in in vitro and/or in vivo studies [16,[62][63][64][65]. As the concentration in the colon is much higher than in the circulation with concentration ranging from 46 to 479 µmol/L in human faecal water [59,66], some effects exerted at high doses may still be physiological [67].…”

Modulators affecting the immune dialogue between human immune and colon cancer cells

“…Polyphenol-rich apple diet administered to rats inhibited TNF-α, iNOS, IL-1β and IL-6 mRNA expression in the colon and diminished the number of CD68 cells [85] . Diet supplemented with cocoa polyphenols feed to rats with experimentally induced colon inflammation decreased the level of the nuclear NF-κB and of the pro-inflammatory enzyme COX-2 [86] . The role of natural products and their phytochemicals in modulation of molecular pathways involved at various stages of tumorigenesis has been summarized by Rajamanickam et al [87] .…”