Complexations of beta-cyclodextrins with naringenin, naringin and catechin: thermodynamic parameters and regulation of mitochondrial functions in vitro

Flavonoids are exogenous phytochemicals with high antioxidative potential. The present work provides the mechanism of the complexations of low water-soluble flavanone naringenin, its glycosylated form naringin, and water-soluble flavan-3-ol catechin with beta-cyclodextrin (beta CD) and hydroxypropyl-beta-cyclodextrin (HP beta CD). The flavonoids studied showed high affinity in the interactions with HP beta CD (the association constants K and the stoichiometry N were equal to 8500 +/- 950 M-1 and 0.85 +/- 0.05, 9400 +/- 1200 M-1 and 1.7 +/- 0.10, 7550 +/- 600 M-1 and 1.25 +/- 0.05 in the case of naringenin, naringin and catechin, respectively). The formations of the complexes with beta-cyclodextrins markedly increased the water solubility of naringenin and naringin. The flavonoid-HP beta CD complexations were exothermic (Delta H < 0) and spontaneous (Delta G < 0). The naringenin and naringin complexations with HP beta CD were entropy-driven, and the catechin complexation was enthalpy-driven. Flavonoid molecules dispersed in the HP beta CD structure during complexations. The flavonoid-HP beta CD associations demonstrated enthalpy-entropy compensation. Naringenin (5-50 mu M) and, to a lesser extent, catechin inhibited the respiration of isolated rat liver mitochondria. Naringenin, naringin and catechin (5-25 mu M) increased the rate of Ca2+-induced mitochondrial permeability transition. The complexations with HP beta CD did not significantly influence the effects of the flavonoids on respiration and enhanced the effects on mitochondrial permeability transition.