title: Apple polyphenols extract (APE) improves colon damage in a rat model of colitis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Rats with trinitrobenzensulphonic acid-induced colitis were treated daily with rectal administration of apple polyphenols 10(-4) M 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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University of Naples, Italy. dargenio@unina.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Argenio
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mazzone
authors.forename: Concetta
authors.initials: C
authors.lastname: Tuccillo
authors.forename: Maria T
authors.initials: MT
authors.lastname: Ribecco
authors.forename: Giulia
authors.initials: G
authors.lastname: Graziani
authors.forename: Antonietta G
authors.initials: AG
authors.lastname: Gravina
authors.forename: Sergio
authors.initials: S
authors.lastname: Caserta
authors.forename: Stefano
authors.initials: S
authors.lastname: Guido
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fogliano
authors.forename: Nicola
authors.initials: N
authors.lastname: Caporaso
authors.forename: Marco
authors.initials: M
authors.lastname: Romano
mesh_terms: D000818:Animals; D002154:Calpain / Q000187:drug effects / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D027845:Malus; D051379:Mice; D041681:NIH 3T3 Cells; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D017208:Rats, Wistar; D011503:Transglutaminases / Q000187:drug effects / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D059808:Polyphenols; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid; D051546:Cyclooxygenase 2; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D002154:Calpain; D019204:GTP-Binding Proteins