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 RESEARCH ARTICLE
Year : 2015  |  Volume : 47  |  Issue : 3  |  Page : 292-298

A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats


1 Deptartment of Pharmacology, Physiology and Atherosclerosis Research Centers, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran
2 Deptartment of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran
3 Pain and Physiology Research Centers, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran
4 Deptartment of Physiology, Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran
5 Deptartment of Physiology, School of Veterinary Medicine, University of Shahid Chamran, Ahvaz, Iran

Correspondence Address:
Dr. Behnam Ghorbanzadeh
Deptartment of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.157127

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Objectives: 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. Materials and 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 E 2 (PGE 2 ) 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, PGE 2 , aspartate aminotransferase and alanine aminotransferase, and suppress the protein expression of iNOS, COX-2 enzymes, and attenuated the formation of PGE 2, 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 PGE 2 overproduction.






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