Caffeic acid and ellagic acid ameliorate adjuvant-induced arthritis in rats via targeting inflammatory signals, chitinase-3-like protein-1 and angiogenesis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory arthropathy that principally attacks the joints. The present study aimed to explore the potential anti-arthritic effects of caffeic acid and ellagic acid in adjuvant-induced arthritis, compared to celecoxib. The current study also explored the underlying molecular mechanisms e.g., pro-inflammatory signals including chitinase-3-like protein-1 (CHI3L1); a glycoprotein that correlates with RA joint destruction besides angiogenesis, oxidative stres and apoptosis. Interestingly, caffeic and ellagic acids attenuated the severity of arthritis with comparable efficacy to celecoxib. Both agents effectively mitigated paw edema and inflammatory cell infiltration and protected the joint tissues against pannus formation along with cartilage and bone destruction. Notably, they also lowered the paw expression of NF-κB and the downstream effector CHI3L1 and its synthesis inducer IL-1β. They also lowered the levels of the tissue remodeling factor MMP-9 and the angiogenic signal VEGF in rat paws. Both agents also suppressed serum oxidative stress via diminishing lipid peroxides and nitric oxide together with augmentation of reduced glutathione in arthritic animals. Regarding apoptosis, they attenuated paw caspase-3 levels, favoring cell survival. Together, these favorable findings may advocate the use of caffeic and ellagic acids as adjunct modalities for the management of RA to mitigate joint damage.

Keywords

• Caffeic acid
• Ellagic acid
• Adjuvant arthritis
• CHI3L1
• Inflammation
• Angiogenesis