cellular uptake of quercetin and luteolin and their effects on monoamine oxidase-a in human neuroblastoma sh-sy5y cells

Monoamine oxidase-A (MAO-A) is the main enzyme in the metabolism of the neurotransmitter serotonin (5-hydroxytryptamine). Elevated activity of MAO-A in the brain may contribute to the pathogenesis of depressive disorders. Plant flavonoids, such as flavonol quercetin and flavone luteolin, have been suggested to be potential antidepressant compounds because they exert a suppressive effect on the MAO-A reaction. We evaluated the effects of these flavonoids on MAO-A activity and protein level using SH-SY5Y as model serotoninergic nerve cells. Quercetin and luteolin were incorporated into SH-SY5Y cells rapidly and converted to O-methylated derivatives. Luteolin accumulated in cells after 24-h incubation, whereas quercetin disappeared completely from cell fractions and culture medium. Addition of ascorbic acid prevented the disappearance of quercetin and allowed it to exert its cytotoxicity (similar to luteolin) at >10 μM. Luteolin and quercetin were incorporated into mitochondria fractions within 1-h incubation and attenuated MAO-A activity slightly but significantly. After 24-h incubation, luteolin attenuated MAO-A activity, but quercetin needed ascorbic acid for its attenuation. Neither luteolin nor quercetin significantly affected MAO-A protein level. These data suggest that luteolin and quercetin can be direct inhibitors of MAO-A in nerve cells by targeting mitochondria.