Detalles: Oleuropein (OL), an olive tree secoiridoid, and its peracetylated derivate (Per OL) have exhibited several beneficial effects reducing acute inflammatory responses on LPS stimulated macrophages. The present study was designed to evaluate the effects of both dietary OL and Per OL supplementations on collagen induced arthritis (CIA) murine model. Three weeks old DBA 1/J male mice were fed from weaning with 0.05 percent (w/w) OL, 0.05 percent or 0.025 percent Per OL. After six weeks of pre treatment, arthritis was induced by bovine collagen type II by tail base injection (day 0) and mice received a booster injection on day 21. Mice were sacrificed 42 days after first immunization. Then, blood was recollected and paws were histological and biochemically processed. OL and Per OL experimental diets significantly prevented histological damage and arthritic score development in RA. In addition, serum collagen oligomeric matrix protein (COMP) and metalloproteinase 3 (MMP) 3 as well as proinflammatory cytokines levels in paw homogenates (including tumor necrosis factor (TNF) a, interleukin (IL) 1b, IL 6, IL 17 and interferon (IFN) y were significantly ameliorated in those animals fed with dietary secoiridoids. Mitogen activated protein kinases (MAPKs) and nuclear transcription factor kappa-B (NF kB) activations were drastically down regulated whereas nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase 1 (HO 1) protein expressions were significantly up regulated in those mice fed with OL and Per OL diets. These results reveal, for the first time, the anti inflammatory effect of a diet supplemented with OL and Per OL in an experimental murine model of CIA, which was accompanied by a significant reduction in the pro inflammatory markers studied (COMP, MMP 3, TNF a, IL 1b, IL 6, IL 17 and IFN y). The mechanisms involved could be related to an activation of the antioxidant pathway Nrf2/HO 1 and an inhibition of MAP kinases and NF kB signaling pathways activations.

On the other hand, we studied the effects of both OL and Per OL diets supplemented diets in a model of pristane induced systemic lupus erythematosus (SLE) in BALB / c mice. Mice received an intraperitoneal injection of pristane or saline according to the experimental groups and were fed with experimental diets enriched with OL and Per OL. Changes in cytokines levels and pro inflammatory markers were evaluated by the ELISA assay. Changes in the protein expression of inducible nitric oxide synthase (iNOS), microsomal prostaglandin E synthase 1 (mPGEs 1) as well as HO 1, nuclear factor Nrf2, p38 protein kinases, C jun NH2 terminal kinase (JNK) and extracellular signal regulated kinase (ERK), signal transduction factor and activator of transcription (STAT) 3, NF kB and inflammasome NLRP3 activation were determined using the Western Blot.

Both OL and Per OL dietary treatments significantly reduced kidney damage and reduced serum MMP 3 and renal prostaglandin E2 (PGE2) levels. Our studies indicated that OL and Per OL enriched diets produced an increase in the expression of the antioxidant pathway Nrf2 / HO 1 which was accompanied by a decrease in the activation of the Janus kinases and signal transducer and activator of transcription (JAK / STAT), MAPKs, NF B and inflammasome NLRP3 proteins.

In conclusion, dietary supplementation with OL and Per OL could serve as the basis for the development of new nutritional strategies for the prevention of RA. In addition, these results also suggest that dietary supplementation with OL and Per OL could constitute a new alternative therapeutic approach as a preventive or palliative of nephritis in the management of SLE.