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Article

Rhubarb-Derived Extracellular Vesicles Mitigate Oxidative Stress and Metabolic Dysfunction in an Alzheimer’s Cellular Model

1
Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy
2
Centro di Digitalizzazione del Patrimonio Culturale (CeDiPa), University of Perugia, 06123 Perugia, Italy
3
Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey
4
Centro di Eccellenza Materiali Innovativi Nanostrutturati (CEMIN), University of Perugia, Via del Giochetto, 06123 Perugia, Italy
*
Author to whom correspondence should be addressed.
Nutrients 2025, 17(23), 3771; https://doi.org/10.3390/nu17233771 (registering DOI)
Submission received: 31 October 2025 / Revised: 27 November 2025 / Accepted: 28 November 2025 / Published: 30 November 2025

Abstract

Background/Objectives: Extracellular vesicles derived from edible plants have emerged as bioactive nanostructures with potential therapeutic and nutraceutical properties and are currently being investigated as natural carriers for the treatment of oxidative stress-induced damage and oxidative stress-related diseases, including neurodegenerative disorders such as Alzheimer’s disease (AD). Recent studies suggest that PDEVs exhibit high stability within the gastrointestinal tract and selective tissue-targeting abilities, facilitating the efficient delivery of bioactive molecules. Methods: This study investigates the antioxidant effects of Rheum rhabarbarum-derived EVs by assessing the antioxidant activity through different in vitro assays and their effects on oxidative stress and energy metabolism in the cellular model of Alzheimer’s disease. Results: Rhubarb-derived EVs showed measurable antioxidant capacity in chemical assays and were non-toxic under the tested conditions. Treatment reduced intracellular ROS levels and modulated oxidative stress-related proteins, suggesting a potential protective effect against oxidative damage. Moreover, metabolic analysis revealed a decrease in glycolytic activity, indicating a potential restoration of cellular bioenergetic homeostasis. Conclusions: These results provide preliminary evidence supporting the nutraceutical interest of rhubarb-derived EVs in counteracting oxidative stress, while further studies will be needed to confirm their biological relevance and therapeutic potential.
Keywords: plant-derived extracellular vesicles (PDEVs); oxidative stress; reactive oxygen species (ROS); Alzheimer’s disease (AD); antioxidant activity; drug delivery plant-derived extracellular vesicles (PDEVs); oxidative stress; reactive oxygen species (ROS); Alzheimer’s disease (AD); antioxidant activity; drug delivery

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MDPI and ACS Style

Calzoni, E.; Cusumano, G.; Bertoldi, A.; Alabed, H.B.R.; Pellegrino, R.M.; Buratta, S.; Urbanelli, L.; Zengin, G.; Emiliani, C. Rhubarb-Derived Extracellular Vesicles Mitigate Oxidative Stress and Metabolic Dysfunction in an Alzheimer’s Cellular Model. Nutrients 2025, 17, 3771. https://doi.org/10.3390/nu17233771

AMA Style

Calzoni E, Cusumano G, Bertoldi A, Alabed HBR, Pellegrino RM, Buratta S, Urbanelli L, Zengin G, Emiliani C. Rhubarb-Derived Extracellular Vesicles Mitigate Oxidative Stress and Metabolic Dysfunction in an Alzheimer’s Cellular Model. Nutrients. 2025; 17(23):3771. https://doi.org/10.3390/nu17233771

Chicago/Turabian Style

Calzoni, Eleonora, Gaia Cusumano, Agnese Bertoldi, Husam B. R. Alabed, Roberto Maria Pellegrino, Sandra Buratta, Lorena Urbanelli, Gokhan Zengin, and Carla Emiliani. 2025. "Rhubarb-Derived Extracellular Vesicles Mitigate Oxidative Stress and Metabolic Dysfunction in an Alzheimer’s Cellular Model" Nutrients 17, no. 23: 3771. https://doi.org/10.3390/nu17233771

APA Style

Calzoni, E., Cusumano, G., Bertoldi, A., Alabed, H. B. R., Pellegrino, R. M., Buratta, S., Urbanelli, L., Zengin, G., & Emiliani, C. (2025). Rhubarb-Derived Extracellular Vesicles Mitigate Oxidative Stress and Metabolic Dysfunction in an Alzheimer’s Cellular Model. Nutrients, 17(23), 3771. https://doi.org/10.3390/nu17233771

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