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)-enr...
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-021-02423-z |
| _version_ | 1818326865046142976 |
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| author | Mahadevappa Hemshekhar Vidyanand Anaparti Hani El-Gabalawy Neeloffer Mookherjee |
| author_facet | Mahadevappa Hemshekhar Vidyanand Anaparti Hani El-Gabalawy Neeloffer Mookherjee |
| author_sort | Mahadevappa Hemshekhar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T12:07:10Z |
| format | Article |
| id | doaj.art-7eac2c4395fb456d9b890ed761534bfe |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-13T12:07:10Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-7eac2c4395fb456d9b890ed761534bfe2022-12-21T23:46:55ZengBMCArthritis Research & Therapy1478-63622021-01-0123111510.1186/s13075-021-02423-zA 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 arthritisMahadevappa Hemshekhar0Vidyanand Anaparti1Hani El-Gabalawy2Neeloffer Mookherjee3Manitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of ManitobaManitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of ManitobaManitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of ManitobaManitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of ManitobaAbstract 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.https://doi.org/10.1186/s13075-021-02423-zRheumatoid arthritisInflammationCurcuminVitamin DOmega-3Collagen-induced arthritis |
| spellingShingle | Mahadevappa Hemshekhar Vidyanand Anaparti Hani El-Gabalawy Neeloffer Mookherjee 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 Arthritis Research & Therapy Rheumatoid arthritis Inflammation Curcumin Vitamin D Omega-3 Collagen-induced arthritis |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Rheumatoid arthritis Inflammation Curcumin Vitamin D Omega-3 Collagen-induced arthritis |
| url | https://doi.org/10.1186/s13075-021-02423-z |
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