Most studies on the antioxidant activity of flavonoids like Quercetin (Q) do not consider that it comprises a series of sequential reactions. Therefore, the present study examines how the redox energy flows through the molecule during Q’s antioxidant activity, by combining experimental data with quantum calculations. It appears that several main pathways are possible. Pivotal are subsequently: deprotonation of the 7-OH group; intramolecular hydrogen transfer from the 3-OH group to the 4-Oxygen atom; electron transfer leading to two conformers of the Q radical; deprotonation of the OH groups in the B-ring, leading to three different deprotonated Q radicals; and finally electron transfer of each deprotonated Q radical to form the corresponding quercetin quinones. The quinone in which the carbonyl groups are the most separated has the lowest energy content, and is the most abundant quinone. The pathways are also intertwined. The calculations show that Q can pick up redox energy at various sites of the molecule which explains Q’s ability to scavenge all sorts of reactive oxidizing species. In the described pathways, Q picked up, e.g., two hydroxyl radicals, which can be processed and softened by forming quercetin quinone.

In the antioxidant activity of quercetin (Q), stabilization of the energy in the quercetin radical (Q^•) by delocalization of the unpaired electron (UE) in Q^• is pivotal. The aim of this study is to further examine the delocalization of the UE in Q^•, and to elucidate the importance of the functional groups of Q for the stabilization of the UE by combining experimentally obtained spin resonance spectroscopy (ESR) measurements with theoretical density functional theory (DFT) calculations. The ESR spectrum and DFT calculation of Q^• and structurally related radicals both suggest that the UE of Q^• is mostly delocalized in the B ring and partly on the AC ring. The negatively charged oxygen groups in the B ring (3′ and 4′) of Q^• have an electron-donating effect that attract and stabilize the UE in the B ring. Radicals structurally related to Q^• indicate that the negatively charged oxygen at 4′ has more of an effect on concentrating the UE in ring B than the negatively charged oxygen at 3′. The DFT calculation showed that an OH group at the 3-position of the AC ring is essential for concentrating the radical on the C2–C3 double bond. All these effects help to explain how the high energy of the UE is captured and a stable Q^• is generated, which is pivotal in the antioxidant activity of Q.

In all life forms, opposing forces provide the energy that flows through networks in an organism, which fuels life. In this concept, health is the ability of an organism to maintain the balance between these opposing forces, which creates resilience, and a deranged flow of energy is the basis for diseases. Treatment should focus on adjusting the deranged flow of energy, e.g., by the redox modulating activity of antioxidants. A major group of antioxidants is formed by flavonoids, a group of polyphenolic compounds abundantly present in our diet. The objective here is to review how the redox modulation by flavonoids fits in the various concepts on the mode of action of bioactive compounds, so we can ‘see’ where there is overlap and where the missing links are. Based on this fundament, we should choose our research path aiming to ‘understand’ the redox modulating profile of specific flavonoids, so we can ultimately rationally apply the redox modulating power of flavonoids to improve our health.

Although Western medicine and Eastern medicine are worlds apart, there is a striking overlap in the basic principle of these types of medicine when we look at them from the perspective of energy. In both worlds, opposing forces provide the energy that flows through networks in an organism, which fuels life. In this concept, health is the ability of an organism to maintain the balance between these opposing forces, i.e., homeostasis (West) and harmony (East), which creates resilience. Moreover, strategies used to treat diseases are strikingly alike, namely adjusting the flow of energy by changing the connections in the network. The energy perspective provides a basis to integrate Eastern and Western medicine, and opens new directions for research to get the best of both worlds.