Rheumatoid arthritis (RA) is a systemic chronic inflammatory autoimmune disease that mainly affects the lining of the synovial joints. Synovial inflammation and proliferation, focal bone erosion and wear away of cartilage are the signs of RA. The synovial membrane, which consists of two cell types (Type A and B synoviocytes) and covers most articular surfaces, tendon sheaths, and bursae, becomes hyperplastic in RA. There are an increased number of both types of synoviocytes and infiltration of synovial fluid with immune and inflammatory cells: particularly macrophages, B- and T-lymphocytes, plasma cells, dendritic cells, mast cells and granulocytes observed in this disease.
Articular cartilage is an avascular tissue composed of a specialized matrix of collagens, proteoglycans, and other proteins. The main constituents of synovial fluid Hyaluronan and lubricin involves in lubricating the surface of the articular cartilage. The hyperplastic synovium causes major damage to the cartilage in RA. The structural damage to the mineralized cartilage and subchondral bone is arbitrated by the osteoclasts.
There is an intricate interplay of genetic, environmental and immunologic factors that triggers the development of RA. The disease mechanism involves activation of autoreactive CD4+ T cells by dendritic cells and inflammatory cytokines produced by macrophages. The preclinical stage in RA is appears to be characterized by a breakdown in self-tolerance and is supported by the finding of anti-cyclic citrullinated peptide (anti-CCP) and serum rheumatoid factors (RF) in patient sera.
Number of studies confers that the risk of RA is very high among the smokers. The elevated citrullination of proteins in bronchoalveolar fluid suggests that environmental factors are the cause of inflammation in RA. On The other hand, presence of microbes might alter the immune system sometimes and that could also lead to the commencement of RA.
Both innate and adaptive immunity is activated in rheumatoid arthritis. T-cell activation towards a T helper 1 (TH1)-cell and/or a TH17-cell phenotype is associated with the presence in the synovial tissue of interleukin-15 (IL-15), IL-1, IL-6, transforming growth factor-β (TGFβ), IL-12 and IL-23. In turn, T cells drive inflammation via IL-17 release and by cognate interactions with adjacent macrophages. CD8+ T cells, natural killer cells and B cells might also influence disease pathogenesis.
Cytokines, particularly tumour-necrosis factor (TNF) plays a vital role in regulating inflammation, autoimmunity and articular destruction in the joints of patients with rheumatoid arthritis. Macrophage-derived cytokines including TNF, IL-1, IL-6, IL-15 and IL-18 drive many of the pro-inflammatory pathways in synovial tissue. Cytokines are also responsible for osteoclast maturation and activation. There appears to be a hierarchical function for receptor activator of nuclear factor-κB ligand (RANKL) in this progression together with TNF, IL-17 and IL-1.
Rheumatoid arthritis is not only associated with increased bone loss but also with the decreased bone formation. Bone formation is hindered due to inflammation. TNF-α increases the expression of dickkopf-1 (DKK-1) and in turn suppress the formation of bones. DKK-1 restricts osteoblast differentiation and bone formation by inhibiting Wnt pathway.
Curcumin has a great anti-inflammatory potential and it can suppress the activity of tumour necrosis factor. Studies show that bioavailable form of curcumin can significantly decrease arthritic disease severity and suppress cellular infiltration, in the joints. The collective effect of Curcumin and VO (vitamin D3 and omega-3-fatty acids)-enriched diet considerably enhances the control of clinical symptoms and maximally delays the onset and progression of the disease. In addition, the combined effect of Curcumin and VO-enriched diet significantly decreases serum levels of critical inflammatory mediators like TNF.
Focelite with its proprietary technology is proficient to formulate different curcumin based products with different dosage forms and could be valuable for arthritic conditions.