Apple polyphenols extract (APE) improves colon damage in a rat model of colitis

• Published in: Digestive and liver disease Vol. 44; no. 7; pp. 555 - 562
• Main Authors: D’Argenio, Giuseppe, Mazzone, Giovanna, Tuccillo, Concetta, Ribecco, Maria T., Graziani, Giulia, Gravina, Antonietta G., Caserta, Sergio, Guido, Stefano, Fogliano, Vincenzo, Caporaso, Nicola, Romano, Marco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.07.2012
• Subjects: Animals; Apple polyphenols; Calpain; Calpain - drug effects; Calpain - metabolism; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Colitis - pathology; Cyclooxygenase 2 - drug effects; Cyclooxygenase 2 - metabolism; Gastroenterology and Hepatology; GTP-Binding Proteins - drug effects; GTP-Binding Proteins - metabolism; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Male; Malus; Mice; NIH 3T3 Cells; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Polyphenols - pharmacology; Polyphenols - therapeutic use; Rabbits; Rat colitis; Rats, Wistar; RNA, Messenger - metabolism; Tissue transglutaminase; Transglutaminases - drug effects; Transglutaminases - metabolism; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - metabolism; Tissue transglutaminase; Calpain; Rat colitis; Apple polyphenols
• ISSN: 1590-8658; 1878-3562; 1878-3562
• DOI: 10.1016/j.dld.2012.01.009

Searching for alternative therapies that are effective, safe and less expensive of those currently used for ulcerative colitis, we investigated the efficacy of a polyphenol extract from apple in rat colitis. Rats with trinitrobenzensulphonic acid-induced colitis were treated daily with rectal administration of apple polyphenols 10−4M for 14 days. COX-2, TNF-α, tissue transglutaminase and calpain in colon mucosa samples were assessed by reverse transcription-polymerase chain reaction and western blot analyses. To ascertain the role of tissue transglutaminase in mucosal healing, wounded rat fibroblasts were incubated with cystamine (a tissue transglutaminase activity inhibitor). Colitis was associated with increased COX-2, TNF-α, calpain, and tissue transglutaminase mRNA. The protein expression of COX-2, TNF-α and calpain was increased whilst tissue transglutaminase was decreased. Apple extract treatment reduced the severity of colitis (p<0.05) and restored all the considered biomarkers at the baseline level. Apple polyphenols reduced the degradation of tissue transglutaminase protein occurring through calpain action. Apple polyphenols-treated wounded fibroblast recovered within 24h showing intense immunoreactivity for tissue transglutaminase. The efficacy of apple extract is mediated by its effects on COX-2 and TNF-α. The unbalance between calpain and tissue transglutaminase may play a role in colonic damage and future therapeutic interventions in ulcerative colitis can target this mechanisms.