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

## TL;DR

A combination of saffron, elderberry, and melilotus protects retinal cells from oxidative stress, which is linked to retinal degenerative diseases.

## Contribution

The study demonstrates that a combination of three natural compounds has additive protective effects against oxidative stress in retinal cells.

## Key findings

- Pretreatment with saffron or the combination reduced oxidative stress and improved cell viability in ARPE-19 cells exposed to H2O2.
- The combination activated the NRF2 pathway and was more effective than saffron alone in preventing caspase-1 activation.
- The mix enhanced SOD2 expression and reduced inflammation markers like IL-1β and LDH activity.

## Abstract

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-1β 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.