Inhibition of Ulcerative Colitis in Mice after Oral Administration of a Polyphenol-Enriched Cocoa Extract Is Mediated by the Inhibition of STAT1 and STAT3 Phosphorylation in Colon Cells

• Published in: Journal of agricultural and food chemistry Vol. 59; no. 12; pp. 6474 - 6483
• Main Authors: Andújar, Isabel, Recio, Ma Carmen, Giner, Rosa Ma, Cienfuegos-Jovellanos, Elena, Laghi, Sara, Muguerza, Begoña, Ríos, José Luis
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 22.06.2011
• Subjects: Animals; anti-inflammatory activity; Bioactive Constituents; Biological and medical sciences; Cacao - chemistry; catechin; Cell Line; colitis; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - genetics; Colitis, Ulcerative - metabolism; colon; Disease Models, Animal; Down-Regulation - drug effects; Female; Flavonoids - administration & dosage; Food industries; Fundamental and applied biological sciences. Psychology; Humans; Mice; Mice, Inbred BALB C; nitric oxide; oral administration; phenolic compounds; Phenols - administration & dosage; phosphorylation; Phosphorylation - drug effects; Plant Extracts - administration & dosage; Polyphenols; sodium sulfate; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; transcription factors; polyphenols; ulcerative colitis; Theobroma cacao; cocoa; inflammatory bowel disease; Phosphorylation; Digestive system; Rodentia; Gut; Oral administration; Extract; Cocoa; Inflammatory disease; Vertebrata; Polyphenol; Mammalia; Mouse; Digestive diseases; Intestinal disease; Colitis; Colon; Inhibition; Cell
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf2008925

We studied a polyphenol-enriched cocoa extract (PCE) with epicatechin, procyanidin B2, catechin, and procyanidin B1 as the major phenolics for its anti-inflammatory properties against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. PCE reduced colon damage, with significant reductions in both the extent and the severity of the inflammation as well as in crypt damage and leukocyte infiltration in the mucosa. Analysis ex vivo showed clear decreases in the production of nitric oxide, cyclooxygenase-2, pSTAT-3, and pSTAT1α, with NF-κB p65 production being slightly reduced. Moreover, NF-κB activation was reduced in RAW 264.7 cells in vitro. In conclusion, the inhibitory effect of PCE on acute UC induced by DSS in mice was attenuated by oral administration of PCE obtained from cocoa. This effect is principally due to the inhibition of transcription factors STAT1 and STAT3 in intestinal cells, with NF-κB inhibition also being implicated.