Naringenin as an opener of mitochondrial potassium channels in dermal fibroblasts

Abstract

Flavonoids belong to a large group of polyphenolic compounds that are widely present in plants. Certain flavonoids, including naringenin, have cytoprotective properties. Although the antioxidant effect has long been thought to be a crucial factor accounting for the cellular effects of flavonoids, mitochondrial channels have emerged recently as targets for cytoprotective strategies. In the present study, we characterized interactions between naringenin and the mitochondrial potassium (mitoBK_C_a and mitoK_ATP ) channels recently described in dermal fibroblasts. With the use of the patch-clamp technique and mitoplasts isolated from primary human dermal fibroblast cells, our study shows that naringenin in micromolar concentrations leads to an increase in mitoBK_C_a channel activity. The opening probability of the channel decreased from 0.97 in the control conditions (200 μmol/L Ca²⁺ ) to 0.06 at a low Ca²⁺ level (1 μmol/L) and increased to 0.85 after the application of 10 μmol/L naringenin. Additionally, the activity of the mitoK_ATP channel increased following the application of 10 μmol/L naringenin. To investigate the effects of naringenin on mitochondrial function, the oxygen consumption of dermal fibroblast cells was measured in potassium-containing media. The addition of naringenin significantly and dose-dependently increased the respiratory rate from 5.8 ± 0.2 to 14.0 ± 0.6 nmol O₂ × min^-1 × mg protein^-1 . Additionally, a Raman spectroscopy analysis of skin penetration indicated that the naringenin was distributed in all skin layers, including the epidermis and dermis. In this study, we demonstrated that a flavonoid, naringenin, can activate two potassium channels present in the inner mitochondrial membrane of dermal fibroblasts.