Combination of Saffron (Crocus sativus), Elderberry (Sambucus nigra L.) and Melilotus officinalis Protects ARPE-19 Cells from Oxidative Stress

Oxidative stress is considered a common underlying mechanism in many retinal degenerative diseases and is often associated with inflammation. The use of dietary supplements containing Saffron has beneficial effects in ocular diseases, though the molecular mechanisms are still unclear. In this study, we investigated how Saffron can exert protective effects against oxidative damage in retinal pigment epithelial cells (ARPE-19) and whether its combination with Elderberry and Melilotus may have additive beneficial effects. ARPE-19 cells were pretreated with Saffron alone or in a mix containing Saffron, Elderberry and Melilotus, then exposed to hydrogen peroxide (H2O2) for 3 h. Afterwards, we evaluated cell viability, oxidative stress and inflammatory status. Our results showed that H2O2 reduced cell viability and total glutathione levels, while increasing caspase-3, caspase-1 and LDH activity. Moreover, H2O2 triggered ROS production, glutathione oxidation and IL-1 beta secretion. Pretreatments with Saffron alone or with the mix counteract these damaging effects by improving cell viability, reducing oxidative stress and enhancing SOD2 expression. Pretreatment with the mix activated the NRF2 pathway and was more effective than Saffron alone in preventing caspase-1 activation. These findings suggest that the combination of Saffron, Elderberry and Melilotus could have therapeutic potential in the prevention and treatment of retinal degenerative diseases.