Oleocanthal mitigates CoCl2-induced oxidative damage and apoptosis via regulating MAPK pathway in human retinal pigment epithelial cells.

Retinal hypoxia causes severe visual impairment and dysfunction in retinal pigment epithelial (RPE) cells, triggering a cascade of events leading to cellular apoptosis. Oxidative stress induced by hypoxia plays a significant role in the development of retinal diseases; however, the precise pathogenesis remains unclear. Oleocanthal, a phenolic compound in extra virgin olive oil, is known for its diverse biological properties. This study aims to investigate the potential anti-oxidative effects of oleocanthal against CoCl₂-induced hypoxia in ARPE-19 cells. The cell culture model enabled the evaluation of apoptosis, DNA damage, and ROS levels using MTT assay, Western blot, Annexin V/PI staining, JC-1 staining, MitoSOX, H₂DCFDA, immunocytochemistry, and comet assays. Our results showed that oleocanthal effectively protected RPE cells against CoCl₂-induced damage by enhancing cell viability, reducing DNA damage, and decreasing ROS levels. Moreover, oleocanthal attenuated CoCl₂-induced MMP loss by elevating the JC-1 aggregate/monomer ratio. Furthermore, CoCl₂-induced cell apoptosis via up-regulating MAPK signaling, while oleocanthal mitigated this effect. These findings shed light on the molecular mechanisms underlying oleocanthal's protection against oxidative stress induced by hypoxia, offering potential insights for the development of novel therapeutic agents for retinal hypoxia.