Oleuropein inhibits the IL-1β-induced expression of inflammatory mediators by suppressing the activation of NF-κB and MAPKs in human osteoarthritis chondrocytes

Abstract

Osteoarthritis (OA) is the most common form of joint disease and is widespread in the elderly population and is characterized by erosion of articular cartilage, subchondral bone sclerosis and synovitis. Oleuropein (OL), a secoiridoid, is considered as the most prevalent phenolic component in olive leaves and seeds, pulp and peel of unripe olives and has been shown to have potent anti-inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of OL on human OA chondrocytes. Human OA chondrocytes were pretreated with OL (10, 50 and 100 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. The production of NO, PGE2, MMP-1, MMP-13, and ADAMTS-5 was evaluated by the Griess reaction and ELISA assays. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP13, ADAMTS-5, aggrecan, and collagen-II was measured by using real-time PCR. The protein expressions of COX-2, iNOS, p65, IκB-α, JNK, p-JNK, ERK, p-ERK, p38, and p-p38 were tested by using western blot. We found that OL significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-13, and ADAMTS-5; and degradation of aggrecan and collagen-II. Furthermore, OL dramatically suppressed IL-1β-stimulated NF-κB and MAPK activation. Immunofluorescence staining demonstrated that OL could suppress IL-1β-induced phosphorylation of p65 nuclear translocation. These results indicate that the therapeutic effect of OL on OA is accomplished through the inhibition of both NF-κB and MAPK signaling pathways. Altogether, our findings provide the evidence to develop OL as a potential therapeutic agent for patients with OA.

Evaluation of the effect of oleuropein on alveolar bone loss, inflammation, and apoptosis in experimental periodontitis

“…also supported these results demonstrating a down‐regulation of MAPK and NF‐KB pathway, decreased TNF‐α, IL‐6, MMP‐1, MMP‐3, and COX‐2 levels in IL‐1β‐induced synovial fibroblast cells . Not only fibroblasts but also human osteoarthritis chondrocytes subjected to oleuropein exhibited suppressed NF‐KB and MAPK activation and decreased COX‐2, iNOS, MMP‐1, and MMP‐13 expressions . All of these findings indicate a robust anti‐inflammatory efficacy of oleuropein, which is also revealed in the present study by decreased total inflammatory cell counts in oleuropein‐treated rats.…”

“…However, while increased levels were observed in the periodontitis group compared to the control groups, there were no differences in the iNOS and CD68 expressions in the oleuropein groups. Contrarily to the literature, no significant difference was observed with oleuropein treatment . CD68 can be considered as an indicator of accumulated macrophage and monocyte lineage cells, and increased levels in the periodontitis indicate increased inflammation …”

“…However, while increased levels were observed in the periodontitis group compared to the control groups, there were no differences in the iNOS and CD68 expressions in the oleuropein groups. Contrarily to the literature, no significant difference was observed with oleuropein treatment 44.…”

“…Recently, Wozniak et al demonstrated that oleuropein decreased p38 MAPK, ERK1/2, and JNK and prevented the translocation of NF-KB from cytosol to nucleus which is critical for the activation of NF-KB 42. Castejon et al also supported these results demonstrat-, and MMP-13 expressions 44. All of these findings indicate a robust anti-inflammatory efficacy of oleuropein, which is also revealed in the present study by decreased total inflammatory cell counts in oleuropein-treated rats.…”

Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and cartilage regeneration in osteoarthritis

“…Although oleuropein was reported to protect from OA progression [69][70][71][72][73] , there was no solid evidence about the underlying molecular mechanisms involved in this effect.…”