Assuntos
Quinase 3 da Glicogênio Sintase/genética , Polimorfismo Genético , Esquizofrenia/genética , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Medicina Baseada em Evidências , Frequência do Gene , Predisposição Genética para Doença , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Fenótipo , Medição de Risco , Fatores de Risco , Esquizofrenia/tratamento farmacológico , Esquizofrenia/enzimologia , Resultado do TratamentoRESUMO
Monoamine oxidases (MAO) are mitochondrial enzymes that catalyze the oxidation of monoamines in multiple tissues, including the brain. Elevated MAO activity has long been implicated in the etiology of depression, anxiety, and neurodegenerative disease, fuelling the search for inhibitors in the prevention and treatment of these disorders. We hypothesized that emerging neuroprotective effects of anthocyanins from berry fruits may be explained by an affinity of these polyphenols for MAO isoforms A or B. Using a luminometric MAO assay, 25 anthocyanidins, anthocyanidin-3-glycosides, anthocyanidin-3,5-diglucosides, proanthocyanidins, and phenolic metabolites were examined. For MAO A and B, IC(50) values in the low micromolar range were reached by anthocyanidins and anthocyanidin-3-glycosides, as opposed to values in the low millimolar range for phenolic acids. Kinetic analyses, performed with cyanidin and cyanidin-3-glucoside, indicated a competitive interaction of cyanidin with MAO A plus a mixed competitive and non-competitive mode of interaction of cyanidin with MAO B and of cyanidin-3-glucoside with both enzyme isoforms. Thus anthocyanins and their aglycons achieve MAO inhibition in vitro that is compatible with central nervous functionalities. For extrapolation of the present findings to in vivo effects, future studies will need to address in more detail the bioavailability of these dietary constituents.
