A bioavailable form of curcumin, in combination with vitamin-D- and omega-3-enriched diet, modifies disease onset and outcomes in a murine model of collagen-induced arthritis

Abstract

Objective Curcumin (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. Methods Male 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. Results CUR 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. Conclusion This 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.

Can Studying Genetically Predisposed Individuals Inform Prevention Strategies for RA?

“…Anti-inflammatory effects of dietary supplements, either individually or when used in combination, are manifold as we showed previously in a murine model of collagen-induced arthritis [55]. In animals with arthritis, curcumin alone or in combination with vitamin D and omega-3 fatty acids significantly reduced disease severity and suppressed cartilage degradation, apart from inhibiting the expression of multiple inflammatory proteins including cytokines, chemokines, and matrix metalloproteinases [55]. Diet also shapes the diversity and composition of the gut microbiome, which in turn primes the mucosal immune system, maintains immune homeostasis in the host and regulates gut permeability and integrity of the intestinal barrier.…”

“…Beneficial effect of dietary components primarily stems from their ability to modulate inflammation either through having a direct effect on the underlying pathways that regulate disease processes or by restoring gut dysbiosis. Anti-inflammatory effects of dietary supplements, either individually or when used in combination, are manifold as we showed previously in a murine model of collagen-induced arthritis [55]. In animals with arthritis, curcumin alone or in combination with vitamin D and omega-3 fatty acids significantly reduced disease severity and suppressed cartilage degradation, apart from inhibiting the expression of multiple inflammatory proteins including cytokines, chemokines, and matrix metalloproteinases [55].…”

“…With these considerations, our research group is planning a prospective clinical trial to investigate the use of curcumin, omega-3, and vitamin D (COD) to modulate RAassociated autoimmunity in Indigenous peoples. Murine models of arthritis suggest that COD can modulate onset and disease activity of arthritis, which supports the biological plausibility of this intervention [55]. Using a randomized, blinded cross-over design has the advantage of ensuring all participants will receive the active intervention treatment, with each individual serving as their own control, which also enhances the statistical power of the analysis [66].…”

Edible Bioactive Film with Curcumin: A Potential “Functional” Packaging?

“…For cardiovascular diseases, the mechanism of action of curcuminoids is associated with the regulation of oxidative stress, apoptosis suppression, and anti-inflammatory activity [ 64 ]. The anti-inflammatory activity of curcuminoids and the modulation of key molecules, such as kinases, also play a role in inflammation regulation and swelling of joint regions in a disease known as arthritis [ 65 ]. Similarly, the anti-obesity activity of curcumin is attributed to anti-inflammatory responses, oxidative stress balance, and endogenous antioxidant enzyme expression [ 66 ].…”

Bioactive compounds of turmeric and their pharmacological effect

“…Curcumin has been demonstrated to have anti-arthritic properties in patients with osteoarthritis and rheumatoid arthritis in several investigations (Henrotin et al, 2013). Moreover, a combination of curcumin, vitamin D3, and omega-3 fatty acids significantly delayed the onset and severity of collagen-induced arthritis (Hemshekhar et al, 2021). Notably, analgesics, steroids, and non-steroidal anti-inflammatory medications (NSAIDs) are currently used to treat arthritis, and they alleviate symptoms such as extreme pain and inflammation (Daily et al, 2016).…”