title: Inhibition of TNF-α, and NF-κB and JNK pathways accounts for the prophylactic action of the natural phenolic, allylpyrocatechol against indomethacin gastropathy.
abstract: BACKGROUND
  The gastro-intestinal disorders, induced by the NSAIDs including indomethacin (IND) remain unresolved medical problems. Herein, we disclose allylpyrocatechol (APC) as a potential agent against IND-gastropathy and rationalize its action mechanistically.
  
  
  METHODS
  Mice were pre-treated with APC for 1h followed by IND (18mgkg(-1)) administration, and the ulcer-prevention capacity of APC was evaluated on the 3rd day by histology. Its effect on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COX, prostaglandins, growth factors and their receptors) and signaling parameters (NF-κB and MAPKs) were assessed by immunoblots/mRNA, and ELISA at the time points of their maximal changes due to IND administration.
  
  
  RESULTS
  IND induced oxidative stress, triggering mucosal TNF-α that activated NF-κB and JNK MAPK signaling in mice. These increased the pro-inflammatory biochemical parameters, but reduced the healing factors. APC reversed all the adverse effects to prevent gastric ulceration. APC (5mgkg(-1)), trolox (50mgkg(-1)) and NAC (250mgkg(-1)) showed similar protection that was better than that by misoprostol (5μgkg(-1)) and omeprazole (3mgkg(-1)).
  
  
  CONCLUSIONS
  The anti-ulcer effect of APC can be primarily attributed to its antioxidant action that helped in controlling various inflammatory parameters and augmenting angiogenesis.
  
  
  CONCLUSIONS
  Given that APC is an effective, non-toxic antioxidant with appreciable natural abundance, further evaluation of its pharmacokinetics and dynamics would help in promoting it as a new anti-inflammatory agent.
authors.affiliation: Department of Biochemistry, Dr. B.C. Roy Post Graduate Institute of Basic Medical Sciences, Kolkata, India.
authors.forename: Sudhir K
authors.initials: SK
authors.lastname: Yadav
authors.forename: Biplab
authors.initials: B
authors.lastname: Adhikary
authors.forename: Sandip K
authors.initials: SK
authors.lastname: Bandyopadhyay
authors.forename: Subrata
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D007213:Indomethacin / Q000009:adverse effects* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D016595:Misoprostol / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D031721:Piper betle / Q000737:chemistry*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D002396:Catechols; D014409:Tumor Necrosis Factor-alpha; C523074:allylpyrocatechol; D016595:Misoprostol; D009853:Omeprazole; D007213:Indomethacin