C-Ring Structure-Dependent Redox Properties of Flavonoids Regulate the Expression of Bioactivity

(-)-Epicatechin (EC), taxifolin (Tax), and quercetin (Q) are flavonoids with different C-ring structures. We compared their physicochemical properties and biological activities. The comparison of their stability and redox properties was conducted at mildly acidic or neutral conditions mimicking the plant vacuole or gut, and their sympathetic hyperactivation ability was examined using catecholamine (CA) excretion and blood flow. At pH 5, flavonoids were stable, but at pH 7, their retention rates decreased in the order EC > Q > Tax. LC-MS analysis detected brown oxidized oligomers in EC, while Tax and Q primarily yielded degradation products. All flavonoids exhibited O₂^•- scavenging activity after incubation at pH 5. At pH 7 after 45-min, EC and Tax promoted O₂^•-, while Q only scavenged O₂^•- after 24-hr incubation, EC's properties decreased but Tax's properties enhanced. Computational chemistry analysis indicated EC has higher reactivity compared to Tax and Q. EC caused a significant increase in CA excretion and blood flow, which were not observed with Tax or Q or 24-h cultured EC. These results suggest that the C-ring structure of flavonoids plays a crucial role in their stability and redox properties. Furthermore, reactive oxygen species generated by flavonoids in the gut may exert beneficial effects through sympathetic activation.