Lemon-derived nanovesicles achieve antioxidant and anti-inflammatory effects activating the AhR/Nrf2 signaling pathway

In the last years, extracellular vesicles (EVs) from different plant matrices have been isolated and gained the interest of the scientific community for their intriguing biological properties. In this study, we isolated and characterized nano- vesicles from lemon juice (LNVs) and evaluated their antioxidant effects. We tested LNV antioxidant activity using human dermal fibroblasts that were pre- treated with LNVs for 24 h and then stimulated with hydrogen peroxide (H2O2) and UVB irradiation. We found that LNV pre-treatment reduced ROS levels in fi- broblasts stimulated with H2O2 and UVB. This reduction was associated with the activation of the AhR/Nrf2 signaling pathway, whose protein expression and nu- clear localization was increased in fibroblasts treated with LNVs. By using zebra- fish embryos as in vivo model, we confirmed the antioxidant effects of LNVs. We found that LNVs reduced ROS levels and neutrophil migration in zebrafish em- bryos stimulated with LPS.