Hemshekhar Mahadevappa, Anaparti Vidyanand, El-Gabalawy Hani, Mookherjee Neeloffer
Manitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, 799 John Buhler Research Centre, 715 McDermot Ave, Winnipeg, MB, Canada.
Division of Rheumatology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
Arthritis Res Ther. 2021 Jan 25;23(1):39. doi: 10.1186/s13075-021-02423-z.
Curcumin (CUR), vitamin D (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.
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.
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.
This study provides proof-of-concept that the combination of bioavailable CUR, vitamin D, 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.
姜黄素（CUR）、维生素D（D3）和ω-3脂肪酸（O3FA）各自可调节关节炎中的炎症和疼痛。尽管这些补充剂被广泛使用，但其联合作用尚未明确。在本研究中，我们在胶原诱导的关节炎（CIA）小鼠模型中研究了富含D3和O3FA（VO）的饮食与高生物利用度形式的CUR（Cureit/Acumin™）联合使用的效果。
雄性DBA/1J小鼠适应富含VO的饮食，并用牛Ⅱ型胶原（CII）进行攻击。从CII攻击开始，每天通过口服灌胃给予生物可利用的CUR。通过监测关节厚度和标准化临床评分来确定疾病严重程度。通过组织学评估关节中的细胞浸润和软骨降解，通过Meso Scale Discovery多重分析测定血清细胞因子，通过蛋白质印迹法检测关节基质金属蛋白酶。
单独使用CUR可使疾病严重程度显著降低约60%。在食用富含VO饮食的CIA小鼠中给予CUR可使疾病严重程度降低>80%，并最大程度地延迟疾病发作和进展。一些改善疾病的作用单独由CUR介导，例如，抑制血清抗胶原抗体以及减少CIA小鼠关节中的细胞浸润和MMP丰度。尽管单独使用CUR可抑制CIA小鼠血清中的炎性细胞因子，但CUR与VO饮食联合使用可显著增强对TNF、IFN-γ和MCP-1的抑制作用（与CUR相比增加>2倍），所有这些都已知与类风湿关节炎发病机制有关。
本研究提供了概念验证，即生物可利用的CUR、维生素D和O3FA联合使用可显著延迟CIA的发展和严重程度。这些发现为系统评估这些广泛可用的补充剂在有发展为未来类风湿关节炎风险的个体中提供了理论依据。
