title: A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats.
abstract: OBJECTIVE
  Ellagic acid (EA) has shown antinociceptive and anti-inflammatory effects. Inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) enzymes and also cytokines play a key role in many inflammatory conditions. This study was aimed to investigate the mechanisms involved in the anti-inflammatory effect of EA.
  
  
  METHODS
  Carrageenan-induced mouse paw edema model was used for induction of inflammation.
  
  
  RESULTS
  The results showed that intraplantar injection of carrageenan led to time-dependent development of peripheral inflammation, which resulted in a significant increase in the levels of tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) β, nitric oxide (NO) and prostaglandin E2 (PGE2) and also iNOS and COX-2 protein expression in inflamed paw. However, systemic administration of EA (1-30 mg/kg, intraperitoneal [i.p.]) could reduce edema in a dose-dependent fashion in inflamed rat paws with ED50 value 8.41 (5.26-14.76) mg/kg. It decreased the serum concentration of NO, PGE2, aspartate aminotransferase and alanine aminotransferase, and suppress the protein expression of iNOS, COX-2 enzymes, and attenuated the formation of PGE2, TNF-α and IL-1 β in inflamed paw tissue. We also demonstrated that EA significantly decreased the malondialdehyde (MDA) level in liver at 5 h after carrageenan injection. Moreover, histopathological studies indicated that EA significantly diminished migration of polymorphonuclear leukocytes into site of inflammation, as did indomethacin.
  
  
  CONCLUSIONS
  Collectively, the anti-inflammatory mechanisms of EA might be related to the decrease in the level of MDA, iNOS, and COX-2 in the edema paw via the suppression of pro-inflammatory cytokines (TNFα, IL1 β), NO and PGE2 overproduction.
authors.affiliation: Deptartment of Pharmacology, Physiology and Atherosclerosis Research Centers, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Mansouri
authors.affiliation: Deptartment of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
authors.forename: Ali Asghar
authors.initials: AA
authors.lastname: Hemmati
authors.affiliation: Pain and Physiology Research Centers, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
authors.forename: Bahareh
authors.initials: B
authors.lastname: Naghizadeh
authors.affiliation: Deptartment of Physiology, Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
authors.forename: Seyyed Ali
authors.initials: SA
authors.lastname: Mard
authors.affiliation: Deptartment of Physiology, School of Veterinary Medicine, University of Shahid Chamran, Ahvaz, Iran.
authors.forename: Anahita
authors.initials: A
authors.lastname: Rezaie
authors.affiliation: Deptartment of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
authors.forename: Behnam
authors.initials: B
authors.lastname: Ghorbanzadeh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D004610:Ellagic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D004610:Ellagic Acid; D009569:Nitric Oxide; D008315:Malondialdehyde; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: Carrageenan; Rat; ellagic acid; inducible nitric oxide synthase; prostaglandin E2