Protein-bound Vaccinium fruit polyphenols decrease IgE binding to peanut allergens and RBL-2H3 mast cell degranulation in vitro

Peanut allergy is a worldwide health concern. In this study, the natural binding properties of plant-derived polyphenols to proteins was leveraged to produce stable protein-polyphenol complexes comprised of peanut proteins and cranberry (Vaccinium macrocarpon Ait.) or lowbush blueberry (Vaccinium angustifolium Ait.) pomace polyphenols. Protein-bound and free polyphenols were characterized and quantified by multistep extraction of polyphenols from protein-polyphenol complexes. Immunoblotting was performed with peanut-allergic plasma to determine peanut protein-specific IgE binding to unmodified peanut protein, or to peanut protein-polyphenol complexes. In an allergen model system, RBL-2H3 mast cells were exposed to peanut protein-polyphenol complexes and evaluated for their inhibitory activity on ionomycin-induced degranulation (a-hexosaminidase and histamine). Among the evaluated polyphenolic compounds from protein-polyphenol complex eluates, quercetin, - in aglycone or glycosidic form was the main phytochemical identified to be covalently bound to peanut proteins. Peanut protein-bound cranberry and blueberry polyphenols significantly decreased IgE binding to peanut proteins at p < 0.05 (38% and 31% decrease, respectively). Sensitized RBL-2H3 cells challenged with antigen and ionomycin in the presence of protein-cranberry and blueberry polyphenol complexes showed a significant (p < 0.05) reduction in histamine and a-hexosaminidase release (histamine: 65.5% and 65.8% decrease; beta-hexosaminidase: 60.7% and 45.4% decrease, respectively). The modification of peanut proteins with cranberry or blueberry polyphenols led to the formation of peanut protein-polyphenol complexes with significantly reduced allergenic potential. Future trials are warranted to investigate the immunomodulatory mechanisms of these protein-polyphenol complexes and the role of quercetin in their hypoallergenic potential.