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

Ornella Urzì; Marco Cafora; Nima Rabienezhad Ganji; Vincenza Tinnirello; Roberta Gasparro; Samuele Raccosta; Mauro Manno; Anna Maria Corsale; Alice Conigliaro; Anna Pistocchi; Stefania Raimondo; Riccardo Alessandro

doi:10.1016/j.isci.2023.107041

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

iScience. 2023 Jun 7;26(7):107041. doi: 10.1016/j.isci.2023.107041. eCollection 2023 Jul 21.

Affiliations

¹ Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata (Bi.N.D), sezione di Biologia e Genetica, Università degli Studi di Palermo, 90133 Palermo, Italy.
² Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, LITA, Via Fratelli Cervi 93, Segrate, 20090 Milano, Italy.
³ Istituto di Biofisica, Consiglio Nazionale delle Ricerche, 90146 Palermo, Italy.
⁴ Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP Paolo Giaccone, Palermo, Italy.
⁵ Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, 90146 Palermo, Italy.

Abstract

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 nanovesicles 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 fibroblasts stimulated with H₂O₂ and UVB. This reduction was associated with the activation of the AhR/Nrf2 signaling pathway, whose protein expression and nuclear localization was increased in fibroblasts treated with LNVs. By using zebrafish embryos as in vivo model, we confirmed the antioxidant effects of LNVs. We found that LNVs reduced ROS levels and neutrophil migration in zebrafish embryos stimulated with LPS.

Keywords: Cell biology; Immunology; Molecular biology.