Phytochemicals as potential antidotes for targeting NF-κB in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune destructive arthropathy prevalent among people in the age group of 40-70 years. RA induces severe pain, swelling and stiffness of joints resulting in bone damage. RA leads to reduced life expectancy when left untreated. RA is characterized by synovial hyperplasia, infiltration of inflammatory cells resulting in formation of pannus. Synovial hyperplasia is mediated by proinflammatory cytokines, notably IL-1 and TNF-α. NF-κB is a predominant transcription factor in amplifying the inflammatory response. The translocation of activated NF-κB into the nucleus triggers the transcription of several genes that induce proinflammatory cytokine production. The inhibition of NF-κB translocation aids blocking the activation of proinflammatory cascades. The quest for more effective and side-effect free treatment for RA unveiled phytochemicals as efficacious and promising. Phytochemicals have been a source of therapeutic substances for many ailments from ancient times. Their therapeutic ability helps in developing potent and safe drugs targeting immune inflammatory diseases driven by NF-κB including RA. This review highlights the importance of NF-κB inflammatory cascade in RA so as to elucidate the crucial role of phytochemicals that inhibit the activity of NF-κB.

Keywords: NF-κB; Phytochemicals; Rheumatoid arthritis; Synovial hyperplasia.

Fig. 1

Various therapies for RA treatment. COX cyclooxygenase, PGE2 prostaglandin E2, MMPs matrix metalloproteinases, DMARDs disease-modifying antirheumatic drugs, NSAIDs nonsteroidal anti-inflammatory drugs, FLS fibroblast-like synoviocytes, TNF-α tumor necrosis factor alpha

Fig. 2

NF-κB signaling cascade. NEMO NF-κB essential modulator

Fig. 3

Structures of phytochemicals inhibiting NF-κB