Myricetin suppresses whey protein allergenicity: In vitro and in vivo study

Reducing the allergenicity of milk-derived proteins is essential for the development of hypoallergenic dairy products. This study was designed to test the hypothesis that myricetin attenuates the allergenicity of whey protein by masking immunoreactive epitopes and modulating immune responses In this study, the effects of myricetin on whey protein allergenicity were evaluated using in vitro and in vivo models. Twenty-seven dietary polyphenols were screened for their ability to inhibit β-lactoglobulin antigenicity using an indirect enzyme-linked immunosorbent assay, and myricetin was identified as the most effective compound. Molecular docking analysis and free thiol group determination suggested that myricetin preferentially interacted with the free thiol group of cysteine 121, suggesting epitope masking as a potential mechanism. In a BALB/c mouse model of whey protein–induced allergy, dietary administration of whey protein combined with myricetin reduced serum mast cell protease-1, antigen-specific immunoglobulin G, and type 2 helper T-cell-associated cytokines, compared with whey protein alone. In addition, myricetin supplementation altered the composition of the intestinal microbiota. These findings support our hypothesis that myricetin can reduce the allergenicity of whey protein, likely through epitope masking and immune-modulatory effects involving the gut microbiota, and highlight its potential application as a natural strategy for producing dairy products with reduced allergenic potential. • Dietary polyphenols were associated with reduced IgE binding to whey protein in vitro. • Myricetin showed the strongest IgE-binding inhibition among screened polyphenols. • Myricetin–whey protein interactions suggested epitope masking as a potential mechanism. • Myricetin treatment was associated with reduced allergic response markers in mice. • Acute mast cell activation markers were reduced following myricetin supplementation. • Myricetin was associated with gut microbiota shifts linked to allergic sensitization.