Anti-arthritic effects of polyunsaturated fatty acid–rich supplementation combined with selective soluble epoxide hydrolase inhibitors in a collagen-induced arthritis mouse model

OBJECTIVES: Polyunsaturated fatty acids (PUFAs) are healthy fats that contain a double carbon bond. They are made up of omega (ω)-3 and ω-6 PUFAs, where ω-3 PUFAs exhibit beneficial effects, such as the suppression of cardiovascular events and the improvement of abnormal lipid metabolism. However, their effects on rheumatoid arthritis (RA) are unclear. Epoxy fatty acids, which are intermediate metabolites of ω-6 and ω-3 PUFAs, are formed through the action of cytochrome P and possess anti-inflammatory properties. However, they are quickly converted into their inactive forms by soluble epoxide hydrolase. METHODS: The protective effects of ω-3 and ω-6 PUFAs on arthritic symptoms with or without soluble epoxide hydrolase inhibitors (sEHis) were investigated in a collagen-induced arthritis mouse model. RESULTS: The group treated with a combination of ω-3 PUFAs and sEHi showed a marked inhibition of arthritis compared to the other groups. Analysis of the faecal flora before the onset of arthritis showed an inverse correlation between the arthritis score and the relative abundance of Lactococcus, suggesting that changes in the intestinal flora in the preclinical stage may influence the onset of arthritis. CONCLUSIONS: This study highlights the potential of ω-3 PUFAs combined with sEHi as the novel protective effect for RA.