{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:38:14Z","timestamp":1785418694460,"version":"3.56.0"},"reference-count":75,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014NextGenerationEU","award":["ECS00000041\u2014VITALITY\u2014CUP J97G22000170005"],"award-info":[{"award-number":["ECS00000041\u2014VITALITY\u2014CUP J97G22000170005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2019s 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\u2019s 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.<\/jats:p>","DOI":"10.3390\/nu17233771","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T10:34:01Z","timestamp":1764758041000},"page":"3771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Rhubarb-Derived Extracellular Vesicles Mitigate Oxidative Stress and Metabolic Dysfunction in an Alzheimer\u2019s Cellular Model"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2876-952X","authenticated-orcid":false,"given":"Eleonora","family":"Calzoni","sequence":"first","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4216-4902","authenticated-orcid":false,"given":"Gaia","family":"Cusumano","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1033-2940","authenticated-orcid":false,"given":"Agnese","family":"Bertoldi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-088X","authenticated-orcid":false,"given":"Husam B. R.","family":"Alabed","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy"},{"name":"Centro di Digitalizzazione del Patrimonio Culturale (CeDiPa), University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5594-383X","authenticated-orcid":false,"given":"Roberto Maria","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Buratta","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0621-8476","authenticated-orcid":false,"given":"Lorena","family":"Urbanelli","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6548-7823","authenticated-orcid":false,"given":"Gokhan","family":"Zengin","sequence":"additional","affiliation":[{"name":"Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Emiliani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06100 Perugia, Italy"},{"name":"Centro di Eccellenza Materiali Innovativi Nanostrutturati (CEMIN), University of Perugia, Via del Giochetto, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sun, X., and Li, X. 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