Daidzein as an IKK-β inhibitor for the management of arthritis: In-vitro and in-vivo approach

Abstract

Rheumatoid arthritis is an autoimmune disorder where the immune system mistakenly attacks the synovium (the lining of the membranes that surround the joints). Chronic inflammation leads to joint damage, cartilage loss, and bone erosion. The exact cause of RA is not fully understood. Nuclear factor kappa β (NF-κβ) functions as a transcription factor for a variety of cytokines, cell adhesion molecules, and enzymes that are involved in the destructive mechanisms of rheumatoid arthritis. The purpose of this study is to characterise the efficacy of “Daidzein” as an IkappaB kinase-beta (IKK-β) inhibitor in collagen-induced arthritis (CIA) model in mice. Arthritis was induced in Balb/C male mice through subcutaneous immunisation with bovine type II collagen on days 0 and 21. Daidzein was administered orally every day after the onset of the disease. The incidence and severity of the disease were clinically assessed throughout the study, and biochemical testing was performed at the conclusion (Day 42). In-vitro findings of the study demonstrated Daidzein as potent inhibitor of IKK-β with IC50 value of 2.32 µM and 3.77 µM in IKK-β and NF-κ β translocation assay. Furthermore, Daidzein (dose range of 10-100 mg/kg, p.o.) was effective in reducing disease incidence and clinical signs in a dose-dependent manner, with an ED₅₀ value of 83.52 mg/kg. The finding of the present study demonstrate dose-dependent efficacy in terms of both disease severity (clinical scoring) and inflammatory markers (biochemical evaluation of the serum and joints).  IKK-β has been reported to play an important role in the pathogenesis of arthritis, and inhibitors of this enzyme represent a promising target for the development of novel treatments for arthritis and other inflammatory conditions. Finding of the present study suggests “Daidzein” represents an novel inhibitor of IKK-β with promising anti-inflammatory activity