Eicosapentaenoic acid and docosapentaenoic acid monoglycerides are more potent than docosahexaenoic acid monoglyceride to resolve inflammation in a rheumatoid arthritis model.

Abstract

INTRODUCTION:

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines and eicosanoids involved in RA pathogenesis. The aim of this study was to determine the therapeutic potential of ω3 monoglyceride (MAG-ω3) compounds in an in vivo rat model of RA induced by Complete Freund's Adjuvant (CFA).

METHOD:

CFA rats were untreated or treated per os with three specific compounds, namely, MAG-docosahexaenoic acid (MAG-DHA), MAG-eicosapentaenoic acid (MAG-EPA) and MAG-docosapentaenoic acid (MAG-DPA). Morphological and histological analyses, as well as pro-inflammatory marker levels were determined following MAG-ω3 treatments.

RESULTS:

Morphological and histological analyses revealed that MAG-EPA and MAG-DPA exhibited strong activity in reducing the progression and severity of arthritic disease in CFA rats. Following MAG-EPA and MAG-DPA treatments, plasma levels of the pro-inflammatory cytokines; interleukin 17A (IL-17A), IL-1β, IL-6 and tumor necrosis factor α (TNFα) were markedly lower when compared to CFA-untreated rats. Results also revealed a decreased activation of p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-kappa B (NFκB) pathways correlated with a reduced expression of TNFα, cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2) and MMP-9 in paw homogenates derived from MAG-EPA and MAG-DPA-treated rats. Of interest, the combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in CFA rats.

CONCLUSION:

Altogether, the present data suggest that MAG-EPA, without vitamin E, represents a new potential therapeutic strategy for resolving inflammation in arthritis.

• Authors: Caroline Morin, Pierre U Blier, Samuel Fortin
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 17 Pg. 142 (May 29 2015) ISSN: 1478-6362 [Electronic] England
• PMID: 26022389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids, Unsaturated
• Interleukin-17
• Interleukin-1beta
• Interleukin-6
• Monoglycerides
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Docosahexaenoic Acids
• Eicosapentaenoic Acid
• Cyclooxygenase 2
• p38 Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• docosapentaenoic acid

Topics

• Animals
• Arthritis, Experimental (blood, drug therapy, metabolism)
• Arthritis, Rheumatoid (blood, drug therapy, metabolism)
• Blotting, Western
• Cyclooxygenase 2 (metabolism)
• Docosahexaenoic Acids (pharmacology)
• Eicosapentaenoic Acid (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Fatty Acids, Unsaturated (pharmacology)
• Female
• Inflammation (blood, drug therapy, metabolism)
• Interleukin-17 (blood)
• Interleukin-1beta (blood)
• Interleukin-6 (blood)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Monoglycerides (pharmacology)
• NF-kappa B (metabolism)
• Rats, Inbred Lew
• Severity of Illness Index
• Tumor Necrosis Factor-alpha (blood, metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)