Protective effects of lemon nanovesicles: evidence of the Nrf2/HO-1 pathway contribution from in vitro hepatocytes and in vivo high-fat diet-fed rats

Roberta Gasparro; Giuditta Gambino; Giulia Duca; Danila Di Majo; Valentina Di Liberto; Vincenza Tinnirello; Giulia Urone; Nicolò Ricciardi; Monica Frinchi; Nima Rabienezhad Ganji; Giuseppe Vergilio; Francesco Paolo Zummo; Francesca Rappa; Simona Fontana; Alice Conigliaro; Pierangelo Sardo; Giuseppe Ferraro; Riccardo Alessandro; Stefania Raimondo

doi:10.1016/j.biopha.2024.117532

Protective effects of lemon nanovesicles: evidence of the Nrf2/HO-1 pathway contribution from in vitro hepatocytes and in vivo high-fat diet-fed rats

Biomed Pharmacother. 2024 Oct 8:180:117532. doi: 10.1016/j.biopha.2024.117532. Online ahead of print.

Authors

Roberta Gasparro¹, Giuditta Gambino², Giulia Duca¹, Danila Di Majo², Valentina Di Liberto², Vincenza Tinnirello¹, Giulia Urone², Nicolò Ricciardi², Monica Frinchi², Nima Rabienezhad Ganji¹, Giuseppe Vergilio³, Francesco Paolo Zummo³, Francesca Rappa⁴, Simona Fontana¹, Alice Conigliaro⁵, Pierangelo Sardo², Giuseppe Ferraro², Riccardo Alessandro⁶, Stefania Raimondo⁷

Affiliations

¹ Department of Biomedicine, Neurosciences and Advanced Diagnostics (Bi.N.D), University of Palermo, Section of Biology and Genetics, Palermo 90133, Italy.
² Department of Biomedicine, Neurosciences and Advanced Diagnostics (Bi.N.D), University of Palermo, Section of Human Physiology, Palermo 90134, Italy.
³ Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Human Anatomy and Histology, University of Palermo, Palermo 90127, Italy.
⁴ Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Human Anatomy and Histology, University of Palermo, Palermo 90127, Italy; The Institute of Translational Pharmacology, National Research Council of Italy (CNR), 90146 Palermo, Italy.
⁵ Department of Biomedicine, Neurosciences and Advanced Diagnostics (Bi.N.D), University of Palermo, Section of Biology and Genetics, Palermo 90133, Italy; ATeN (Advanced Technologies Network) Center, Viale Delle Scienze, University of Palermo, 90128, Palermo, Italy; Navhetec s.r.l., Spinoff of the University of Palermo, Palermo, Italy.
⁶ Department of Biomedicine, Neurosciences and Advanced Diagnostics (Bi.N.D), University of Palermo, Section of Biology and Genetics, Palermo 90133, Italy; Navhetec s.r.l., Spinoff of the University of Palermo, Palermo, Italy; Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), Palermo 90146, Italy.
⁷ Department of Biomedicine, Neurosciences and Advanced Diagnostics (Bi.N.D), University of Palermo, Section of Biology and Genetics, Palermo 90133, Italy; Navhetec s.r.l., Spinoff of the University of Palermo, Palermo, Italy. Electronic address: stefania.raimondo@unipa.it.

PMID: 39383731
DOI: 10.1016/j.biopha.2024.117532

Abstract

The cross-talk between plant-derived nanovesicles (PDNVs) and mammalian cells has been explored by several investigations, underlining the capability of these natural nanovesicles to regulate several molecular pathways. Additionally, PDNVs possess biological proprieties that make them applicable against pathological conditions, such as hepatic diseases. In this study we explored the antioxidant properties of lemon-derived nanovesicles, isolated at laboratory (LNVs) and industrial scale (iLNVs) in human healthy hepatocytes (THLE-2) and in metabolic syndrome induced by a high-fat diet (HFD) in the rat. Our findings demonstrate that in THLE-2 cells, LNVs and iLNVs decrease ROS production and upregulate the expression of antioxidant mediators, Nrf2 and HO-1. Furthermore, the in vivo assessment reveals that the oral administration of iLNVs improves glucose tolerance and lipid dysmetabolism, ameliorates biometric parameters and systemic redox homeostasis, and upregulates Nrf2/HO-1 signaling in HFD rat liver. Consequently, we believe LNVs/iLNVs might be a promising approach for managing hepatic and dysmetabolic disorders.

Keywords: High-fat diet fed rats; Lemon-derived nanovesicles; Liver; Metabolic syndrome; Oxidative stress.