title: Antioxidant activity, cellular bioavailability, and iron and calcium management of neuroprotective and nonneuroprotective flavones.
abstract: Few studies have been undertaken on the relationship of the structure of flavones and neuroprotection. Previously, we described the structural determinants of the neuroprotective activity of some natural flavones in cerebellar granule neurons in culture against an oxidative insult (H2O2). In the present work, we analyzed anti-oxidant activity, cellular iron, and Ca(2+) levels and cellular bioavailability of neuroprotective and nonneuroprotective flavones in the same experimental paradigm. Oxidative cellular damage produced by H2O2 was prevented by all of the studied flavones with rather similar potency for all of them. Labile Iron Pool was neither affected by protective nor nonprotective flavones. Intracellular Ca(2+) homeostasis was not affected by protective flavones either. Nonetheless, fisetin, the nonprotective flavone, decreased Ca(2+) levels modifying Ca(2+) homeostasis. Methylation of the catechol group, although weakens anti-oxidant capacity, keeps the neuroprotective capacity with less degradation and lower toxicity, constituting promising structural alternatives as leads for the design of neuroprotective molecules.
authors: UNESCO CHAIR: "Neuroprotective Natural Compounds", Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Av. Italia 3318, 11600, Montevideo, Uruguay, caroliecheverry@gmail.com.
authors: Carolina
authors: C
authors: Echeverry
authors: Florencia
authors: F
authors: Arredondo
authors: Marcela
authors: M
authors: Martínez
authors: Juan Andrés
authors: JA
authors: Abin-Carriquiry
authors: Jacob
authors: J
authors: Midiwo
authors: Federico
authors: F
authors: Dajas
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D005419:Flavonoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D007501:Iron; D002118:Calcium