Omega-3 docosahexaenoic acid and procyanidins inhibit cyclo-oxygenase activity and attenuate NF- kappaB activation through a p105/p50 regulatory mechanism in macrophage inflammation.

摘要

The inflammatory response has been implicated in the pathogenesis of many chronic diseases. Along these lines, the modulation of inflammation by consuming bioactive compounds in foods, such as omega-3 fatty acids or procyanidins, is considered to be a powerful tool to promote good health. In this study, the administration of DHA (docosahexaenoic acid) and B₁, B₂ and C₁ procyanidins, alone or in combination, was found to prevent the inflammatory response induced by the LPS (lipopolysaccharide) endotoxin in human macrophages and brought them to the homoeostatic state. DHA and B₁ were strong, selective inhibitors of cyclooxygenase 1 activity, with IC₅₀ values of 13.5 and 8.0 muM, respectively. B₂ and C₁ were selective inhibitors of pro-inflammatory cyclooxygenase 2 activity, with IC₅₀ values of 9.7 and 3.3 muM, respectively. Moreover, DHA and procyanidins prevented the activation of the NF- kappaB (nuclear factor kappaB) cascade at both early and late stages with shared mechanisms. These included inhibition of I kappaB alpha (inhibitor of NF- kappaB alpha) phosphorylation, inducing the cytoplasmic retention of pro-inflammatory NF- kappaB proteins through p105 (NF- kappaB1) overexpression, favouring the nuclear translocation of the p50-p50 transcriptional repressor homodimer instead of the p50-p65 pro-inflammatory heterodimer, inhibiting binding of NF- kappaB DNA to kappaB sites and, finally, decreasing the release of NF- kappaB-regulated cytokines and prostaglandins. It is concluded that DHA and procyanidins are strong, selective inhibitors of cyclooxygenase activity and NF- kappaB activation through a p105/p50-dependent regulatory mechanism.