Osteoarthritis (OA), a prevalent degenerative condition, occurs due to the deterioration of joint tissues and cells. Consequently, safeguarding chondrocytes against damage caused by inflammation is an area of future research emphasis. There is growing evidence that Ergolide (ERG) has multiple biological functions. Nevertheless, it is still uncertain whether it can hinder the advancement of OA. In this study, we investigate the ERG's potential to reduce inflammation and protect cartilage. ERG treatment in vitro effectively inhibited the excessive production of pro-inflammatory substances, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-α (TNF-α), leading to their complete suppression. Furthermore, ERG suppressed the production of matrix-degrading enzymes (ADAMTS-5) and matrix metalloproteinase 13 (MMP13), consequently impeding the breakdown of extracellular matrix (ECM) and restraining the synthesis of collagenase II and Aggrecan. Through the P38/MAPK pathway, we discovered that ERG hinders the activation of NF-κB in chondrocytes induced by IL-1β. The protective effect of ERG was enhanced by the p38 MAPK inhibitor SB203580. In vivo, ERG further demonstrated protective effects on cartilage in animal models of DMM. In conclusion, the study has discovered that ERG exhibits innovative therapeutic potential in the context of OA.
Keywords: Ergolide; Inflammation; NF-κB; Osteoarthritis; P38/MAPK.
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