title: Quercetin in brain diseases: Potential and limits.
abstract: Quercetin is a ubiquitous flavonoid present in beverages, food and plants that has been demonstrated to have a role in the prevention of neurodegenerative and cerebrovascular diseases. In neuronal culture, quercetin increases survival against oxidative insults. Antioxidation appears to be a necessary but not sufficient condition for its neuroprotective action and modulation of intracellular signaling and transcription factors, increasing the expression of antioxidant and pro survival proteins and modulating inflammation, appears as important for neuronal protection. Quercetin also regulates the activity of kinases, changing the phosphorylation state of target molecules, resulting in modulation of cellular function and gene expression. Concentrations of quercetin higher than 100 μM consistently show cytotoxic and apoptotic effects by its autoxidation and generation of toxic quinones. In vivo, results are controversial with some studies showing neuroprotection by quercetin and others not, requiring a drug delivery system or chronic treatments to show neuroprotective effects. The blood and brain bioavailability of free quercetin after ingestion is a complex and controversial process that produces final low concentrations, a fact that has led to suggestions that metabolites would be active by themselves and/or as pro-drugs that would release the active aglycone in the brain. Available studies show that in normal or low oxidative conditions, chronic treatments with quercetin contributes to re-establish the redox regulation of proteins, transcription factors and survival signaling cascades that promote survival. In the presence of highly oxidative conditions such as in an ischemic tissue, quercetin could become pro-oxidant and toxic. At present, evidence points to quercetin as a preventive molecule for neuropathology when administered in natural matrices such as vegetables and food. More research is needed to support its use as a lead compound in its free form in acute treatments, requiring new pharmaceutical formulations and/or structural changes to limit its pro-oxidant and toxic effects.
authors.affiliation: Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. Electronic address: fdajas@gmail.com.
authors.forename: Federico
authors.initials: F
authors.lastname: Dajas
authors.affiliation: Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Juan Andrés
authors.initials: JA
authors.lastname: Abin-Carriquiry
authors.affiliation: Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Florencia
authors.initials: F
authors.lastname: Arredondo
authors.affiliation: Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Blasina
authors.affiliation: Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Carolina
authors.initials: C
authors.lastname: Echeverry
authors.affiliation: Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Marcela
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Felicia
authors.initials: F
authors.lastname: Rivera
authors.affiliation: Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Lucía
authors.initials: L
authors.lastname: Vaamonde
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D001927:Brain Diseases / Q000188:drug therapy* / Q000378:metabolism*; D005419:Flavonoids / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011794:Quercetin / Q000008:administration & dosage* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D011794:Quercetin
keywords: Brain; Flavonoids; Neuroprotection; Nutraceuticals; Quercetin