Malus domestica fruit-derived vesicles extract protect against upstream cellular hallmarks of vascular inflammation and epithelial barrier dysfunction

Background Dysbiosis 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. Methods ADEVs 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. Results ADEVs 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. Conclusion ADEVs 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.