Effect of Flavonoids on PTP and Dehydrogenase Activity in Liver Mitochondria

The inner mitochondrial membrane contains various ion channels and protein complexes that participate in cellular bioenergetics by synthesizing ATP. In addition, these structures are involved in cellular signaling through the generation of reactive oxygen species, thereby contributing to the regulation of physiological processes and the development of pathological conditions. Thus, mitochondria play a crucial role in the functioning of cells and tissues. Therefore, in in vitro studies, we investigated the effects of various flavonoids on the mPTP of rat liver mitochondria, as well as on the activities of succinate–ferricyanide reductase (succinate dehydrogenase) and NADH–ferricyanide reductase (NADH dehydrogenase). The results demonstrated that flavonoids exert an inhibitory effect on the mPTP of rat liver mitochondria, forming the following order based on their half-maximal inhibitory concentrations: apigenin > quercetin > isorhamnetin > oroxylin A > pulicarin > chrysoeriol > kaempferol > kaempferol-7-O-rhamnoside > hyperoside. Moreover, pre-incubation of liver mitochondria with 50 µM NADH for 10 minutes enhanced the inhibitory effect of flavonoids on the mPTP. Under these conditions, apigenin, oroxylin A, quercetin, kaempferol, chrysoeriol, hyperoside, and pulicarin exhibited strong inhibitory effects, whereas the remaining flavonoids showed weaker inhibition. In addition, at concentrations of 10 and 50 µM, the flavonoids hyperoside, kaempferol, kaempferol-7-O-rhamnoside, isorhamnetin, quercetin, afzelin, and pulicarin increased succinate–ferricyanide reductase activity, while the other flavonoids exhibited very weak or no effect. At the same time, a strong inhibitory effect of quercetin, isorhamnetin, kaempferol-7-O-rhamnoside, hyperoside, and kaempferol on NADH–ferricyanide reductase activity was observed, whereas the remaining studied flavonoids demonstrated only weak inhibitory effects. Overall, the results indicate that the flavonoids investigated in vitro possess distinct and compound-specific properties.