Malus domestica fruit-derived vesicles extract protect against upstream cellular hallmarks of vascular inflammation and epithelial barrier dysfunction
Abstract
BackgroundDysbiosis impairs the intestinal barrier, facilitating the systemic translocation of inflammatory molecules into the bloodstream and ultimately contributing to cardiovascular disease. In this study, apple-derived extracellular vesicles (ADEVs) were evaluated as natural carriers of immunomodulatory signals to non-invasively restore immune homeostasis while preventing vascular inflammation and epithelial barrier dysfunction.MethodsADEVs were isolated from Malus domestica via tangential flow filtration and characterized by particle concentration, size distribution, and total protein content. Vesicle integrity and cargo stability were evaluated across multiple storage temperature assays. The immunomodulatory effects of ADEVs against lipopolysaccharide-induced inflammation were assessed in both in vitro human cell lines and an in vivo mouse model.ResultsADEVs isolated by this scalable purification method, maintained structural integrity, concentration, and size uniformity following cryopreservation. Functional assays revealed that ADEVs significantly fortified the intestinal epithelial barrier, suppressed pro-inflammatory signaling, and prevented endothelial activation, effectively blocking key mechanisms of monocyte recruitment. In the murine model, ADEVs were safely metabolized within hours without accumulation in major organs. Crucially, ADEVs induced a dual polarization of immune cells toward both pro-resolving and functional states, successfully recalibrating systemic immune homeostasis.ConclusionADEVs function as highly efficient, biocompatible carriers of natural regulatory signals that mitigate inflammation responses. By simultaneously reinforcing the intestine barrier and modulating immune activity, ADEVs represent a viable, minimally invasive therapeutic strategy against the upstream cellular drivers of vascular inflammation and epithelial dysfunction.
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BibTeX
@article{cappucci2026malus,
title = {{Malus domestica fruit-derived vesicles extract protect against upstream cellular hallmarks of vascular inflammation and epithelial barrier dysfunction}},
author = {Ilenia Pia Cappucci and Laura Basile and Lucia Sileo and Maria Pia Cavaleri and Luna Ardondi and Ilaria Vitali and Marta Degasperi and Jasmine Chini and Luca Lovatti and Leo Massari and Sonia Missiroli and Paolo Pinton and Barbara Zavan and Letizia Ferroni},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1911938},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1911938},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Malus domestica fruit-derived vesicles extract protect against upstream cellular hallmarks of vascular inflammation and epithelial barrier dysfunction
AU - Ilenia Pia Cappucci
AU - Laura Basile
AU - Lucia Sileo
AU - Maria Pia Cavaleri
AU - Luna Ardondi
AU - Ilaria Vitali
AU - Marta Degasperi
AU - Jasmine Chini
AU - Luca Lovatti
AU - Leo Massari
AU - Sonia Missiroli
AU - Paolo Pinton
AU - Barbara Zavan
AU - Letizia Ferroni
PY - 2026
DA - 2026/11/06
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1911938
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1911938
AB - BackgroundDysbiosis impairs the intestinal barrier, facilitating the systemic translocation of inflammatory molecules into the bloodstream and ultimately contributing to cardiovascular disease. In this study, apple-derived extracellular vesicles (ADEVs) were evaluated as natural carriers of immunomodulatory signals to non-invasively restore immune homeostasis while preventing vascular inflammation and epithelial barrier dysfunction.MethodsADEVs were isolated from Malus domestica via tangential flow filtration and characterized by particle concentration, size distribution, and total protein content. Vesicle integrity and cargo stability were evaluated across multiple storage temperature assays. The immunomodulatory effects of ADEVs against lipopolysaccharide-induced inflammation were assessed in both in vitro human cell lines and an in vivo mouse model.ResultsADEVs isolated by this scalable purification method, maintained structural integrity, concentration, and size uniformity following cryopreservation. Functional assays revealed that ADEVs significantly fortified the intestinal epithelial barrier, suppressed pro-inflammatory signaling, and prevented endothelial activation, effectively blocking key mechanisms of monocyte recruitment. In the murine model, ADEVs were safely metabolized within hours without accumulation in major organs. Crucially, ADEVs induced a dual polarization of immune cells toward both pro-resolving and functional states, successfully recalibrating systemic immune homeostasis.ConclusionADEVs function as highly efficient, biocompatible carriers of natural regulatory signals that mitigate inflammation responses. By simultaneously reinforcing the intestine barrier and modulating immune activity, ADEVs represent a viable, minimally invasive therapeutic strategy against the upstream cellular drivers of vascular inflammation and epithelial dysfunction.
SN - 1663-9812
ER -