Celecoxib, a COX-2 inhibitor, synergistically potentiates the anti-inflammatory activity of docosahexaenoic acid in macrophage cell line.

BACKGROUND: The anti-inflammatory properties of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and non-steroidal anti-inflammatory drugs overlap in many ways. The aim of this study was to examine the individual and synergetic anti-inflammatory effects of celecoxib, EPA and DHA in RAW-264.7 cell line. METHODOLOGY: The cells were exposed to EPA, DHA, celecoxib, rosiglitazone, GW9662 alone or their combination, and stimulated with 5 µg/mL lipopolysaccharide (LPS). Nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and prostaglandin-E2 (PGE2) levels were estimated in the medium using enzyme-linked immunosorbent assays. The cyclooxygenase-2 (COX-2) and inducible Nitric Oxide Synthase (iNOS) expression were analyzed in the cell lysate by immunoblotting. Peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor-κB (NF-κB) transcription factor activation assays were performed in the nuclear extract. RESULTS: Combined treatment of DHA (50 µM) and celecoxib (20 µM) significantly inhibited LPS induced synthesis of NO, TNF-α, IL-6 and PGE2 levels in the cells, compared to the individual treatments. In addition, DHA and celecoxib diminished the COX-2 and iNOS expression in the cells. This was associated with increased PPARγ activity, supressed NF-κB activity in the nucleus. We determined whether GW9662, a specific PPARγ inhibitor, could abolish the anti-inflammatory effect of DHA and celecoxib. GW9662 has abolished the DHA and celecoxib induced PPARγ activation, but did not alter the NF-κB mediated anti-inflammatory effects induced by celecoxib and DHA. Interestingly, EPA did not exhibit any inhibitory effect on these parameters. CONCLUSION: Our results suggest that DHA and celecoxib exhibit anti-inflammatory effect through inhibition of NF-κB, independent of PPARγ. Co-administration of celecoxib and DHA would be promising approach for the treatment of inflammatory diseases.

Medium-chain triglycerides and monounsaturated fatty acids potentiate the beneficial effects of fish oil on selected cardiovascular risk factors in rats.

Fish oil (FO) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to reduce the risk of cardiovascular diseases (CVDs). Little information is known regarding the influence of lipid composition in the background diet on the modulatory effect of FO supplementation on CVDs. The present study was designed to investigate the influence of various background dietary lipids and FO on selected cardiovascular risk factors in rats. Adult Wistar rats were fed semisynthetic diet with FO at 1.0% or 2.0% along with other lipids, namely, medium-chain triacylglycerols (MCTs), monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs) and n-3 PUFAs, for 5 weeks. Some of the potent CVD risk factors were estimated in the rats. FO at 1.0% and 2.0% has significantly reduced serum lipid peroxides, total cholesterol, triglycerides (TAGs), tumor necrosis factor-α, interleukin-6 and C-reactive protein; liver and adipose TAG and cholesterol levels in MCT, MUFA and n-6 PUFA diet groups. Notably, these alterations were comparatively higher in 1.0% FO-substituted MCT and MUFA diet groups. Interestingly, feeding of FO along with n-3 PUFAs did not show additive effect in attenuation of these factors. Serum liver EPA and DHA levels were remarkably elevated in rats fed FO-enriched MCT or MUFA diets. Our results suggest that MCTs or MUFAs in the background diet might promote the beneficial effects of FO on CVDs.