Ellagic acid protects against carrageenan-induced acute inflammation through inhibition of nuclear factor kappa B, inducible cyclooxygenase and proinflammatory cytokines and enhancement of interleukin-10 via an antioxidant mechanism

摘要

There are several hypotheses that explain the process of acute inflammation, including free radical overproduction, pro-inflammatory enzyme activation, and release of pro-inflammatory cytokines. In this study, the protective role of ellagic acid against carrageenan-induced acute inflammation was assessed. In addition, the immunomodulatory action, the antioxidant effects, and the role of COX-2 and NF-κB were also investigated. Inflammation was induced by the injection of 100 μl of 1.5% carrageenan solution. Ellagic acid (10, 25, 50, 100 and 200 mg/kg), indomethacin (10 mg/kg), meloxicam (4 mg/kg), and saline, were injected 2 h before carrageenan injection. The percentage inhibition in the paw weight was calculated. Paws, MDA, NO, GSH, IL-1β, TNF-α, IL-10 and NF-κB mRNA expression were estimated. Formalin fixed hind paws were used for histopathological examination and immunohistochemical staining for COX-2 expression. Ellagic acid, meloxicam and indomethacin reduced paws, edema, MDA and NO formation. In addition, all of them restored the depleted GSH contents in the paws. Ellagic acid, meloxicam and indomethacin reduced NF-κB mRNA expression. Ellagic acid ameliorated COX-2 expression; meloxicam inhibited while indomethacin failed. Both ellagic acid and meloxicam increased IL-10 while indomethacin did not. The docking study revealed a high affinity of ellagic acid towards COX-2. Ellagic acid exhibited a potent anti-inflammatory effect against carrageenan-induced inflammation. The mechanisms of ellagic acid induced protection were proved to be due to reduction of NO, MDA, IL-1β, TNF-α, COX-2 and NF-κB expression and induction of GSH and IL-10 production.