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Antioxidants
Volume 14
Issue 12
10.3390/antiox14121421
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Multifunctional Biological Activity Assessment of Plant-Derived Nanovesicles from Arugula Leaves: In Vitro and In Vivo Studies

by
Lorenza d’Adduzio
1,
Melissa Fanzaga
1,
Davide Marangon
1,
Antonio Carrillo-Vico
2,3,
Ivan Cruz-Chamorro
2,3,4,
Carlotta Bollati
1,
Davide Lecca
1 and
Carmen Lammi
1,*
1
Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy
2
Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Sevilla, 41009 Seville, Spain
3
Instituto de Biomedicina de Sevilla, IBiS (Universidad de Sevilla, HUVR, Junta de Andalucía, CSIC), 41013 Seville, Spain
4
Facultad de Enfermería, Universidad de Castilla-La Mancha, 02071 Albacete, Spain
*
Author to whom correspondence should be addressed.
Antioxidants 2025, 14(12), 1421; https://doi.org/10.3390/antiox14121421
Submission received: 20 October 2025 / Revised: 21 November 2025 / Accepted: 25 November 2025 / Published: 27 November 2025
(This article belongs to the Section Natural and Synthetic Antioxidants)
Versions Notes

Abstract

Plant-derived vesicles (PDVs) represent an emerging class of naturally bioformulated nanocarriers with potential nutraceutical and therapeutic applications. In this study, the multifunctional biological activity of PDVs obtained from Eruca sativa leaves (arugula leaf vesicles, ALVs) was investigated both in vitro and in vivo. In differentiated Caco-2 and HepG2 cells, ALVs exhibited significant antioxidant activity, being rich in polyphenols and organic acids, by reducing intracellular reactive oxygen species (ROS) and modulating key metabolic regulators. ALVs upregulated SREBP-2, LDLR, and phosphorylated AMPK and Akt, leading to enhanced LDL and glucose uptake, while downregulating FASN and PPAR-γ, thereby reducing lipid accumulation. In mice fed a high-fat and high-fructose (HFHF) diet, ALV supplementation improved glucose tolerance and decreased total cholesterol, LDL, and hepatic injury biomarkers (ALT, AST, and LDH) without inducing toxicity. These findings demonstrate that ALVs exert hypocholesterolemic, hypoglycemic, and lipid-lowering effects through coordinated modulation of AMPK/Akt pathways. Overall, ALVs emerge as safe, multifunctional nanovesicles capable of counteracting oxidative stress and metabolic dysfunction, highlighting their potential as innovative bioactive ingredients for functional foods or nutraceutical formulations targeting metabolic syndrome.
Keywords: bioactive plant nanovesicles; antioxidant activity; cholesterol lowering effect; multifunctional activity bioactive plant nanovesicles; antioxidant activity; cholesterol lowering effect; multifunctional activity

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MDPI and ACS Style

d’Adduzio, L.; Fanzaga, M.; Marangon, D.; Carrillo-Vico, A.; Cruz-Chamorro, I.; Bollati, C.; Lecca, D.; Lammi, C. Multifunctional Biological Activity Assessment of Plant-Derived Nanovesicles from Arugula Leaves: In Vitro and In Vivo Studies. Antioxidants 2025, 14, 1421. https://doi.org/10.3390/antiox14121421

AMA Style

d’Adduzio L, Fanzaga M, Marangon D, Carrillo-Vico A, Cruz-Chamorro I, Bollati C, Lecca D, Lammi C. Multifunctional Biological Activity Assessment of Plant-Derived Nanovesicles from Arugula Leaves: In Vitro and In Vivo Studies. Antioxidants. 2025; 14(12):1421. https://doi.org/10.3390/antiox14121421

Chicago/Turabian Style

d’Adduzio, Lorenza, Melissa Fanzaga, Davide Marangon, Antonio Carrillo-Vico, Ivan Cruz-Chamorro, Carlotta Bollati, Davide Lecca, and Carmen Lammi. 2025. "Multifunctional Biological Activity Assessment of Plant-Derived Nanovesicles from Arugula Leaves: In Vitro and In Vivo Studies" Antioxidants 14, no. 12: 1421. https://doi.org/10.3390/antiox14121421

APA Style

d’Adduzio, L., Fanzaga, M., Marangon, D., Carrillo-Vico, A., Cruz-Chamorro, I., Bollati, C., Lecca, D., & Lammi, C. (2025). Multifunctional Biological Activity Assessment of Plant-Derived Nanovesicles from Arugula Leaves: In Vitro and In Vivo Studies. Antioxidants, 14(12), 1421. https://doi.org/10.3390/antiox14121421

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