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

Dig Liver Dis. 2012 Jul;44(7):555-62. doi: 10.1016/j.dld.2012.01.009. Epub 2012 Feb 28.

Abstract

Background and aim: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calpain / drug effects
  • Calpain / metabolism
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism*
  • Colitis / pathology
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / metabolism
  • 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*
  • Protein Glutamine gamma Glutamyltransferase 2
  • RNA, Messenger / metabolism
  • Rabbits
  • Rats, Wistar
  • Transglutaminases / drug effects
  • Transglutaminases / metabolism
  • Trinitrobenzenesulfonic Acid
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Plant Extracts
  • Polyphenols
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Trinitrobenzenesulfonic Acid
  • Cyclooxygenase 2
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • Calpain
  • GTP-Binding Proteins