title: Neuroprotective actions of flavones and flavonols: mechanisms and relationship to flavonoid structural features.
abstract: Epidemiological studies have shown positive preventive action of flavonoids on cardiovascular and neurodegenerative events. Among the six groups in which flavonoids are classified, the flavones and flavonols, based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one) are the most commonly encountered within the families and genera of the higher plants. Numerous studies support a neuroprotective activity of flavones such as luteolin and flavonols such as kaempherol and quercetin in experimental focal ischemia and models of neurodegeneration. Antioxidation, modulation of signaling cascades and gene expression as well as anti-inflammation appear as the main protective mechanisms and mitochondria are a likely main target mediating the preventive actions against oxidative stress. Flavones and flavonols re-establish the redox regulation of proteins, transcription factors and signaling cascades that are otherwise inhibited by elevated oxidative stress. The final survival or death of the neuron depends on flavone and flavonol concentrations, time of exposure and, mainly, metabolic and oxidative neuronal circumstances. Neuroprotection appears to be linked to specific structural motifs, beyond those involved in antioxidation. By themselves or as templates for synthetic compounds, flavone and flavonol molecules show potential as multi-targeted therapeutic tools for protecting the brain. Nonetheless, more research needs to be done on the correlation of potential beneficial effects of flavones and flavonols and their mechanisms of action.
authors.affiliation: Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Avda Italia 3318, 11600, Montevideo, Uruguay. fdajas@gmail.com
authors.forename: Federico
authors.initials: F
authors.lastname: Dajas
authors.forename: Abin-Carriquiry Juan
authors.initials: AC
authors.lastname: Andrés
authors.forename: Arredondo
authors.initials: A
authors.lastname: Florencia
authors.forename: Echeverry
authors.initials: E
authors.lastname: Carolina
authors.forename: Rivera-Megret
authors.initials: RM
authors.lastname: Felicia
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D047309:Flavones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D044948:Flavonols / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009422:Nervous System Diseases / Q000378:metabolism / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D047309:Flavones; D005419:Flavonoids; D044948:Flavonols; D018696:Neuroprotective Agents