Acetyl zingerone ameliorates osteoarthritis by inhibiting chondrocyte programmed cell death.

Abstract

Osteoarthritis (OA) is a degenerative disease that ultimately leads to joint deformity. The pathogenesis of OA is believed to involve abnormal chondrocyte death, with ferroptosis serving a key role in chondrocyte damage. The present study investigated whether acetyl zingerone (AZ), a newly identified antioxidant derived from curcumin, can alleviate the progression of OA. To investigate this, the present study performed various experiments, including crystal violet staining, flow cytometry, immunofluorescence and western blot analysis. In addition, dual validation was performed using invivo and invitro experiments; a mouse OA model was constructed for the invivo experiments, and chondrocytes were used for the invitro experiments. Destabilization of the medial meniscus (DMM) surgery was performed to establish an OA model in mice and IL‑1β was used to induce an OA model invitro. The results indicated that AZ may promote chondrocyte viability and the expression of extracellular matrix components. Furthermore, AZ reduced the occurrence of ferroptosis by promoting the expression of glutathione peroxidase 4, inhibiting cartilage destruction and osteophyte formation, and alleviating damage to articular cartilage caused by DMM surgery. Mechanistically, the activation of nuclear factor erythroid 2‑related factor 2 and heme oxygenase‑1 may be responsible for the anti‑ferroptosis effects of AZ on chondrocytes. These findings indicated that AZ may be considered a promising candidate for OA therapy.