Ellagic acid alleviates adjuvant induced arthritis by modulation of pro- and anti-inflammatory cytokines

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology, but it is now clear that pro-inflammatory cytokines play a central role in its pathogenesis. Ellagic acid (EA) has a variety of biological activities including anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of the present study was to evaluate the potential effect of ellagic acid on the prevention and/or treatment of adjuvant induced arthritis (AIA) model in mice. Ellagic acid treatment was started one week before AIA induction and continued for three weeks after induction of AIA. Ellagic acid treatment significantly (p < 0.01) inhibited foot paw oedematous swelling and attenuated AIA-associated pathology. Ellagic acid significantly (p < 0.01) reduced serum levels of pro-inflammatory cytokines: interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin 17 (IL-17). However, serum levels of IL-10 and interferon γ (IFN-γ) significantly increased (p < 0.01 and p < 0.05, respectively), while serum level of transforming growth factor β (TGF-β) did not significantly alter with EA treatment. In conclusion, these results suggest that EA attenuated AIA-associated pathology in the mouse model by downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines.

Keywords: adjuvant induced arthritis; anti-inflammatory cytokine; ellagic acid; pro-inflammatory cytokine.

Fig. 1

Histopathological evaluation of ellagic acid treatment on adjuvant induced arthritis in mice. Representative results showing the histopathological picture of hind paws and digits of normal control (NC), normal treated (NT), arthritic control (AC) and arthritic treated (AT) mice in H&E (100×) stained sections. The normal histological picture of hind paws joints was presents in both NC and NT mice. AC mice showed synovial hyperplasia, inflammatory cells infiltration, pannus formation, and cartilage destruction; whereas AT mice revealed less severity of arthritis pathology

Fig. 2

Representative photomicrographs showing the histopathological picture of hind paws and digits of arthritic control (AC) and arthritic treated (AT) mice in H&E stained sections (× 400). AC mice showed hyperplastic synovial membrane composed of multiple layers of synoviocytes (AC-a), marked pannus formation and fibroplasia of the underlying connective tissues associated with cartilage erosion and bone resoprption (AC-b), and multiple panni were formed from synovial membrane (AC-c). However, AT mice revealed mild pannus formation, fibroplasias, cartilage erosion and bone resoprption (AT)

Fig. 3

The effect of ellagic acid treatment on the histopathological arthritis score of arthritic control (AC) and arthritic treated (AT) mice. The histopathological score of synovitis, pannus formation, bone resorption and cartilage destruction were examined per grades out of total score 12. Data reported as mean ± SD of 10 mice per each group. ** p < 0.01