Quantum-chemical modeling of the electronic structure of quercetin and inhibition by quercetin and quercetin–hydroxypropyl-β-cyclodextrin complex of lipid peroxidation in mitochondria and red blood cells of rats

Abstract

Quercetin (3,3ʹ,4ʹ,5,7-pentahydroxyflavon), one of the most common and studied flavonoids, possesses the antioxidant activity and demonstrates the pronounced therapeutic potential under a number of pathological conditions. The purpose of this work is to estimate the electronic structure of the quercetin and its semi-quinone radical molecules and to compare the antioxidant activities of quercetin and its inclusion complex with hydroxypropyl-β-cyclodextrin. Generation of maps of the electron density distribution in quercetin and quercetin semi-quinone radical molecules showed that the active electron orbitals (HOMO and LUMO) are delocalized over all phenolic rings providing the radical stabilization. We have showed that quercetin prevents the tert-butyl hydroperoxide-induced lipid peroxidation of erythrocytes (IC50= 25 ± 3 μM) and mitochondrial membranes (IC50= 31 ± 4 μM). The efficiency of quercetin inhibition the reduced glutathione oxidation in erythrocytes and mitochondria is much lower reflecting the lipophilicity of polyphenol. Quercetin also prevented the hypochlorite-induced lysis of red blood cells (IC50= 3 ± 0.5 μM). Our data revealed that the quercetin-hydroxypropyl-β-cyclodex-trin complex is more effective inhibitor of the membrane lipids peroxidation and glutathione oxidation processes.