Identification and computational assessment of novel targeting sites of dexamethasone sodium phosphate for improved efficacy in the management of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a prevalent chronic inflammatory condition. The cause of RA involves a complex system of cytokines and cells that stimulate the growth of synovial cells and cause damage to cartilage and bone. TNF-α is a pivotal pro-inflammatory cytokine in the etiology of RA, whereas glucocorticoids (GCs) are powerful immunomodulator that frequently employed to mitigate of inflammation. Alongside TNF-α, other cytokines including IL-17 and IL-18, as well as inflammatory mediators and enzymes such as COX-2, MMP-7, MMP-9, and MMP-13, significantly contribute to joint inflammation and tissue degradation in RA. Dexamethasone sodium phosphate (DSP) has a significant therapy effect on RA by diminish the regulation of cytokines and inhibiting the function of leukocytes, and fibroblasts. In present study, novel pharmacophore features of DSP has been determined via computational assessment which provide new approaches for management of RA. The docking score values on different receptors for anti-arthritis activity, it is observed that DSP, namely, IL-18, COX-2, MMP-9 and Mineralocorticoid showed the best docking results. It has been found that DSP has some new targeting arability towards Spleen tyrosine kinase (Syk), Interferon (IFN)-γ, Nicotinamide phosphoribosyl transferase (NAMPT) or Visfatin, NF-κB receptors which are responsible for RA regulation. Further, anti-inflammatory assay suggests its anti-arthritic activity and MTT assay divulge its toxicity towards pro-inflammatory macrophages. In order to determine the effectiveness of DSP in treatment of RA, the DSP has been administered to complete Freund's adjuvant (CFA) developed rat. The anti-arthritic impact was evaluated by measuring the arthritic index; hind paw volume, X-ray imaging, and histopathology of ankle joints in arthritic rats.