Onion Peel-Derived Exosome-Like Nanovesicles as a Novel Therapeutic Approach for Inflammatory Bowel Disease

Abstract

Chronic inflammation of the intestinal mucosa and impaired intestinal epithelial barrier integrity are two hallmarks of inflammatory bowel disease (IBD). Given the limitations and side effects of conventional biological therapies, the isolation of plant-derived exosome-like nanoparticles (PDEN) from agri-food byproducts represents a sustainable and biocompatible therapeutic option for the development of novel bioactive platforms. In this study, we successfully extracted nanovesicles from industrial onion (Allium cepa) waste peels (OP-EVs) using a protocol combining enzymatic digestion, differential centrifugation, and ultracentrifugation. Their stable nanoscale size (94.1 ± 1.7 nm mode; 63.0 nm), negative surface charge (-16.3 mV), plant-specific markers (Hsp70, TET8, PEN1), and high encapsulation of bioactive flavonoids and polyphenols were confirmed by NTA, DLS, Western blot and LC-MS/MS analysis. In human colonic epithelial cells (HCECs), OP-EVs were non-cytotoxic and efficiently internalized. OP-EVs significantly reduced pro-inflammatory cytokine production (IL-8, IL-6, and TNF-α) under LPS-induced acute inflammatory stress by reducing MAPK/ERK activation and NF-κB (p65). Additionally, OP-EVs restored E-cadherin expression, suppressed N-cadherin overexpression, and markedly accelerated scratch wound closure to protect mucosal barrier integrity in chronic inflammatory conditions. Collectively, these findings suggest that OP-EVs may represent a potential zero-waste nutraceutical platform capable of sustaining epithelial barrier integrity while lowering mucosal inflammation.