Extra-virgin olive oil phenols hydroxytyrosol and hydroxytyrosol acetate, down-regulate the production of mediators involved in joint erosion in human synovial cells

The hallmark of rheumatoid arthritis (RA) pathology is characterized by both hyperproliferation of synovial fibroblasts (SFs) and massive infiltration of inflammatory immune cells. This study was conducted to evaluate the efficacy of hydroxytyrosol (HTy) and hydroxytyrosol-acetate (HTy-Ac) in regulating IL-1β-induced production of metalloproteases (MMPs) and proinflammatory cytokines in human synovial cell line. Treatment with HTy or HTy-Ac significantly inhibited IL-1β-induced MMPs, tumour necrosis factor (TNF)-α and IL-6 production. IL-1β-up regulation COX-2 and mPGE-1 was downregulated by HTy and HTy-Ac. IL-1β-induced MAPKs phosphorylation and NF-κB activation were inhibited by HTy and HTy-Ac. These results suggest that these EVOO phenols reduce the production of proinflammatory mediators in SW982 cells; these protective effects could be related to the inhibition of MAPKs and NF-κB signalling pathways. Thus, HTy and HTy-Ac might be promising targets for the prevention and management of diseases associated with overactivation of synovial fibroblasts, like RA.