Resveratrol-modified cashew allergens for reduced allergenic potency and enhanced anti-inflammatory potential

Cashew allergy presents a significant challenge for oral immunotherapy (OIT), as current treatment approaches often rely on unmodified allergens that carry a high risk of triggering severe immune responses. To address this challenge, this study explores a novel strategy by conjugating resveratrol to cashew allergens using a free-radical grafting method. The conjugation process, initiated by ascorbic acid and hydrogen peroxide, led to covalent bonding confirmed by reductions in free amino and thiol groups and a notable increase in β-turn content from 39.1% to 49.0%, indicating irreversible structural modification. Immunoblotting demonstrated reduced binding to anti-cashew IgG and human sIgE, further confirming structural modification and suggesting diminished allergenic potential, respectively. Cytotoxicity tests using Caco-2 cells confirmed high biocompatibility up to 1000 μg/mL, while resveratrol conjugation significantly suppressed TNF-α-induced IL-8 secretion, highlighting the anti-inflammatory properties of the conjugates. These findings support the potential of resveratrol-conjugated cashew allergens as safer, multifunctional candidates for next-generation OIT interventions. • Resveratrol modified Cashew allergens increased random coils and β-turns. • Resveratrol enhanced antioxidant function to cashew allergen conjugates. • Anti-inflammatory effect: IL-8 suppressed in TNF-α-stimulated Caco-2 cells. • Reduced IgE binding and basophil degranulation suggested lower allergenicity. • Conjugates showed high bioavailability in Caco-2 epithelial cell model.