Abstract
ObjectiveCurcumin (CUR), vitamin D3 (D3), and omega-3-fatty acids (O3FA) individually modulate inflammation and pain in arthritis. Although these supplements are widely used, their combinatorial effects have not been defined. In this study, we examined the effects of a D3 and O3FA (VO)-enriched diet in conjunction with a highly bioavailable form of CUR (Cureit/Acumin™) in a collagen-induced arthritis (CIA) murine model.MethodsMale DBA/1J mice were acclimatized to VO-enriched diet and challenged with bovine collagen II (CII). Bioavailable CUR was administered daily by oral gavage from the onset of CII challenge. Disease severity was determined by monitoring joint thickness and standardized clinical score. Cellular infiltration and cartilage degradation in the joints were assessed by histology, serum cytokines profiled by Meso Scale Discovery multiplex assay, and joint matrix metalloproteinases examined by western blots.ResultsCUR by itself significantly decreased disease severity by ~ 60%. Administration of CUR in CIA mice taking a VO-enriched diet decreased disease severity by > 80% and maximally delayed disease onset and progression. Some of the disease-modifying effects was mediated by CUR alone, e.g., suppression of serum anti-collagen antibodies and decrease of cellular infiltration and MMP abundance in the joints of CIA mice. Although CUR alone suppressed inflammatory cytokines in serum of CIA mice, the combination of CUR and VO diet significantly enhanced the suppression (> 2-fold compared to CUR) of TNF, IFN-γ, and MCP-1, all known to be associated with RA pathogenesis.ConclusionThis study provides proof-of-concept that the combination of bioavailable CUR, vitamin D3, and O3FA substantially delays the development and severity of CIA. These findings provide a rationale for systematically evaluating these widely available supplements in individuals at risk for developing future RA.
Highlights
Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects nearly 1% of the adult population worldwide [1, 2]
The animals were divided into two groups: one group fed with a standard diet, and the second group was fed a vitamin D3 (10,000 IU/kg of diet) and omega-3-fatty acids (O3FA) (10 g/kg of diet)-enriched diet (VO-enriched diet)
At the completion of the protocol on day 29, we showed that collagen-induced arthritis (CIA) mice on the VO-enriched diet alone had a ~ 35% reduction of clinical scores compared to mice on a normal diet (Fig. 1b)
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects nearly 1% of the adult population worldwide [1, 2] It is characterized by immune-mediated chronic inflammation targeting the synovium of multiple joints which, if not treated early, results in irreversible degradation of the adjacent cartilage and bone leading to progressive deformity and functional loss [1,2,3]. Treatment with the currently available arsenal of diseasemodifying anti-rheumatic drugs (DMARDs), biologics, and Janus-Kinase (JNK) inhibitors, often in combination, has dramatically improved the outcomes of this disease [4, 5]. These treatments are associated with significant immunosuppression, prohibitive cost, and in some cases treatment failure to multiple agents. Several strategies are currently being evaluated in this context, the safety and acceptability of any intervention at the preclinical stage is a key consideration [6, 7]
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