The gastric ulcer-healing action of allylpyrocatechol is mediated by modulation of arginase metabolism and shift of cytokine balance

Eur J Pharmacol. 2009 Jul 1;614(1-3):106-13. doi: 10.1016/j.ejphar.2009.04.046. Epub 2009 May 3.

Abstract

The role of the ariginine-metabolism in the healing action of the Piper betle phenol, allylpyrocatechol (APC) and omeprazole against indomethacin-induced stomach ulceration in mouse was investigated. Indomethacin (18 mg/kg) was found to induce maximum stomach ulceration in Swiss albino mice on the 3rd day of its administration, which was associated with reduced arginase activity (21.6%, P<0.05), endothelial nitric oxide synthase (eNOS) expression (72%, P<0.001), and IL-4 and TGF-beta levels, along with increased inducible nitric oxide synthase (iNOS) (9.3 folds, P<0.001) expression, nitrite (2.29 folds, P<0.001), IL-1beta and IL-6 generation. Besides providing comparable healing as omeprazole (3 mg/kg x 3 days), APC (5 mg/kg x 3 days) shifted the iNOS/NO axis to the arginase/polyamine axis as revealed from the increased arginase activity (73.1%, P<0.001), eNOS expression (67.8%, P<0.001), and reduced iNOS expression (65.6%, P<0.001) and nitrite level (53.2%, P<0.001). These can be attributed to a favourable anti-/pro-inflammatory cytokines ratio, generated by APC. The healing by omeprazole was however, not significantly associated with those parameters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Arginase / metabolism*
  • Arginine / metabolism
  • Catechols / pharmacology*
  • Catechols / therapeutic use*
  • Cytokines / blood
  • Cytokines / metabolism*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Male
  • Mice
  • Mucous Membrane / drug effects
  • Mucous Membrane / enzymology
  • Mucous Membrane / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / metabolism
  • Nitrites / blood
  • Peroxidase / metabolism
  • Stomach Ulcer / blood
  • Stomach Ulcer / drug therapy*
  • Stomach Ulcer / enzymology
  • Stomach Ulcer / metabolism

Substances

  • Anti-Inflammatory Agents
  • Catechols
  • Cytokines
  • Nitrites
  • allylpyrocatechol
  • Nitric Oxide
  • Arginine
  • Peroxidase
  • Nitric Oxide Synthase
  • Arginase