Cellular uptake of quercetin and luteolin and their effects on monoamine oxidase-A in human neuroblastoma SH-SY5Y cells

Abstract

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.

Olive (Olea europaea L.) Biophenols: A Nutriceutical against Oxidative Stress in SH-SY5Y Cells

“…Our results suggest that olive biophenol extracts are superior to the individual olive non-flavonoids and flavonoids for protection of the SH-SY5Y cells against Cu-induced toxicity, which could be a promising therapy for the treatment of AD. Olive flavonoids exhibit relatively poor protection and the possible reason behind their poor activities is that they are susceptible to auto-oxidation and conversion into their O -methylated metabolites, with the lack of a hydroxyl group ultimately leading to slight cytotoxicity to the SH-SY5Y cells [ 67 ].…”

Docking study of flavonoid derivatives as potent inhibitors of influenza H1N1 virus neuraminidase

“…Due to the reported antioxidant, antibacterial and antiviral effects, presence in normal daily diet and minimal side-effects of flavonoids, they are considered useful resources for drug design (8,(18)(19)(20)(21)(22). Initial reports on the use of flavonoids as pharmaceutical compounds emerged in the 1940s, when the potential of these compounds was evaluated in the prevention and treatment of coronary heart disease and for their anti-cancer, anti-inflammatory, antibacterial and antiviral effects (23)(24)(25)(26)(27)(28)(29). Due to the diversity of flavonoids, the use of computational designs and molecular information on flavonoid compounds enables the selection of the optimum compounds in investigations aimed at identifying alternative drugs with greater impact.…”

An amine oxidase gene from mud crab, Scylla paramamosain, regulates the neurotransmitters serotonin and dopamine in vitro

“…Quercetin exerts an inhibitory effect on the mitochondrial MAO-A reaction in the mouse brain by reducing the deamination product of 5-HT [ 72 ]. In a study on human neuroblastoma SH-SY5Y cells, it was also found that the flavonol quercetin could localize to the outer mitochondrial membrane and attenuate MAO-A activity directly in neuronal cells [ 73 ]. In particular, the researchers used docking simulation studies to show that quercetin has a high affinity for the MAO-A protein and to provide the lowest interaction energy configuration of the quercetin and MAO-A complex [ 71 ].…”