A New Peracetylated Oleuropein Derivative Ameliorates Joint Inflammation and Destruction in a Murine Collagen-Induced Arthritis Model via Activation of the Nrf-2/Ho-1 Antioxidant Pathway and Suppression of MAPKs and NF-κB Activation

Abstract

Oleuropein (OL), an olive tree secoiridoid and its peracetylated derivate (Per-OL) haveexhibited several beneficial effects on LPS-stimulated macrophages and murine experimental sys-temic lupus erythematosus (SLE). This study was designed to evaluate dietary Per-OL in comparisonwith OL supplementation effects on collagen-induced arthritis (CIA) murine model. Three-weeks-old DBA-1/J male mice were fed from weaning with a standard commercial diet or experimentalenriched-diets in 0.05 % (w/w) OL, 0.05% and 0.025% Per-OL. After six weeks of pre-treatment, arthri-tis was induced by bovine collagen type II by tail base injection (day 0) and on day 21, mice received abooster injection. Mice were sacrificed 42 days after the first immunization. Both Per-OL and OL dietssignificantly prevented histological damage and arthritic score development, although no statisticallysignificant differences were observed between both compounds. Also, serum collagen oligomericmatrix protein (COMP), metalloprotease (MMP)-3 and pro-inflammatory cytokines levels were ame-liorated in paws from secoiridoids fed animals. Mitogen-activated protein kinases (MAPK)s andnuclear transcription factor-kappa-B (NF-κB) activations were drastically down-regulated whereasnuclear factor E2-related factor 2 (Nrf2) and heme-oxygenase-1 (HO-1) protein expressions wereup-regulated in those mice fed with OL and Per-OL diets. We conclude that both Per-OL and itsparent compound, OL, supplements might provide a basis for developing a new dietary strategy forthe prevention of rheumatoid arthritis.