Abstract
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.
Highlights
Food synergy concept is suggested to explain observations that isolated antioxidants are less bioactive than real foods containing them
The flavonols were represented by quercetin (Q) and its rhamnoside–rutin (R) and flavanones by naringenin (N−) and its neohesperidoside naringin (N+)
These polyphenols differ in the number and location of redox-active hydroxyl groups as well as the ability to form intramolecular H-bonds, i.e., three structural features that may interfere with reducing properties of antioxidant compounds
Summary
Food synergy concept is suggested to explain observations that isolated antioxidants are less bioactive than real foods containing them. It was presumed that these substances once isolated from their natural sources, purified and consumed in the form of dietary supplements containing higher doses than those achievable in the diet could become powerful chemopreventive agents This assumption was confirmed by a large body of evidence coming from studies exploiting various experimental in vitro and in vivo models of chronic diseases, including c ancer[6,7]. Our recent mechanistic investigations involving step-wise reconstitution of cocoa composition of bioactives supported the idea of food synergy, but demonstrated that the biological effects of samples with complex compositions are not just a combination of the activities displayed by individual c omponents[13] All these observations suggested that when considering redox related bioactivities of isolated antioxidants versus their mixtures, the interactions between components must be taken into account. The growing complexity of a mixture of phytochemicals seemed to create a new redox-active substance rather than enrich the mixture with new activities characteristic of the compound added, which is inferred by the food synergy concept
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