Peptide–Polyphenol Interactions: The Antagonistic Effect of Pea Pentapeptide (VNRFR) on the Antioxidant Properties of Quercetin and Rutin in <i>Caenorhabditis elegans</i>

Food-derived peptides and polyphenols have demonstrated antioxidant activities against reactive oxygen species and free radicals. However, little is known about their combined antioxidant capacity when they interact within a mixture. This study investigated the antioxidant capacity of a mixture of flavonoids (quercetin or rutin) and pea protein-derived pentapeptide (VNRFR) in vitro and in vivo using the Caenorhabditis elegans model. Dynamic light scattering, spectroscopic, and molecular docking analysis revealed the formation of peptide–polyphenol complexes, with the polyphenolic aromatic ring and peptide phenylalanine residue interacting noncovalently by π-stacking. The interaction resulted in antagonistic radical scavenging activity in vitro and antioxidative effects in vivo based on the nematode mean lifespan and survival rate, and intracellular reactive oxygen species levels. Notably, the antagonism was more pronounced for rutin due to the additional H-bonding that its rhamnosyl-glucoside moiety formed with the peptide. The findings provide valuable insights into food matrix interactions that affect the antioxidant capacity of nutraceutical mixtures in formulated products.