Interactions between polyphenolic antioxidants quercetin and naringenin dictate the distinctive redox-related chemical and biological behaviour of their mixtures

Food synergy concept is suggested to explain observations that isolated antioxidants are less bioactive than real foods containing them. However, mechanisms behind this discrepancy were hardly studied. Here, we demonstrate the profound impact of interactions between two common food flavonoids (individual: aglycones quercetin-Q and naringenin-N- or their glycosides rutin-R and naringin-N+ vs. mixed: QN- and RN+) on their electrochemical properties and redox-related bioactivities. N- and N+ seemed weak antioxidants individually, yet in both chemical and cellular tests (DPPH and CAA, respectively), they increased reducing activity of mixtures synergistically. In-depth measurements (differential pulse voltammetry) pointed to kinetics of oxidation reaction as decisive factor for antioxidant power. In cellular (HT29 cells) tests, the mixtures exhibited properties of a new substance rather than those of components. Pure flavonoids did not influence proliferation; mixtures stimulated cell growth. Individual flavonoids tended to decrease global DNA methylation with growing concentration; this effect was more pronounced for mixtures, but not concentration-dependent. In nutrigenomic studies, expression of gene set affected by QN- differed entirely from common genes modulated by individual components. These results question the current approach of predicting bioactivity of mixtures based on research with isolated antioxidants.