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

Abstract

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 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: Mohammad Taghi Mansouri, Ali Asghar Hemmati, Bahareh Naghizadeh, Seyyed Ali Mard, Anahita Rezaie, Behnam Ghorbanzadeh
• Journal: Indian journal of pharmacology (Indian J Pharmacol) 2015 May-Jun Vol. 47 Issue 3 Pg. 292-8 ISSN: 1998-3751 [Electronic] India
• PMID: 26069367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Interleukin-1beta
• Tumor Necrosis Factor-alpha
• Ellagic Acid
• Nitric Oxide
• Malondialdehyde
• Carrageenan
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Carrageenan
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Dose-Response Relationship, Drug
• Edema (chemically induced, drug therapy)
• Ellagic Acid (pharmacology, therapeutic use)
• Hindlimb (drug effects, metabolism)
• Inflammation (drug therapy)
• Interleukin-1beta (metabolism)
• Liver (metabolism)
• Male
• Malondialdehyde (metabolism)
• Nitric Oxide (blood)
• Nitric Oxide Synthase Type II
• Rats
• Tumor Necrosis Factor-alpha (metabolism)