title: Clovamide and rosmarinic acid induce neuroprotective effects in in vitro models of neuronal death.
abstract: OBJECTIVE
  Phenolic compounds exert cytoprotective effects; our purpose was to investigate whether the isosteric polyphenolic compounds clovamide and rosmarinic acid are neuroprotective.
  
  
  METHODS
  Three in vitro models of neuronal death were selected: (i) differentiated SH-SY5Y human neuroblastoma cells exposed to tert-butylhydroperoxide (t-BOOH), for oxidative stress; (ii) differentiated SK-N-BE(2) human neuroblastoma cells treated with L-glutamate, for excitotoxicity; and (iii) differentiated SH-SY5Y human neuroblastoma cells exposed to oxygen-glucose deprivation/reoxygenation, for ischaemia-reperfusion. Cell death was evaluated by lactate dehydrogenase measurements in the cell media, while the mechanisms underlying the effects by measuring: (i) t-BOOH-induced glutathione depletion and increase in lipoperoxidation; and (ii) L-glutamate-induced intracellular Ca(2+) overload (fura-2 method) and inducible gene expression (c-fos, c-jun), by reverse transcriptase-PCR. The ability of compounds to modulate nuclear factor-kappaB and peroxisome proliferator-activated receptor-gamma activation was evaluated by Western blot in SH-SY5Y cells not exposed to harmful stimuli.
  
  
  RESULTS
  Both clovamide and rosmarinic acid (10-100 micromol x L(-1)) significantly protected neurons against insults with similar potencies and efficacies. The EC(50) values were in the low micromolar range (0.9-3.7 micromol x L(-1)), while the maximal effects ranged from 40% to -60% protection from cell death over untreated control at 100 micromol x L(-1). These effects are mediated by the prevention of oxidative stress, intracellular Ca(2+) overload and c-fos expression. In addition, rosmarinic acids inhibited nuclear factor-kappaB translocation and increased peroxisome proliferator-activated receptor-gamma expression in SH-SY5Y cells not exposed to harmful stimuli.
  
  
  CONCLUSIONS
  Clovamide and rosmarinic acid are neuroprotective compounds of potential use at the nutritional/pharmaceutical interface.
authors.affiliation: Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche, e Farmacologiche, University of Piemonte Orientale Amedeo Avogadro, 28100 Novara, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Fallarini
authors.forename: G
authors.initials: G
authors.lastname: Miglio
authors.forename: T
authors.initials: T
authors.lastname: Paoletti
authors.forename: A
authors.initials: A
authors.lastname: Minassi
authors.forename: A
authors.initials: A
authors.lastname: Amoruso
authors.forename: C
authors.initials: C
authors.lastname: Bardelli
authors.forename: S
authors.initials: S
authors.lastname: Brunelleschi
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D000097123:Rosmarinic Acid
chemical_list: D002934:Cinnamates; D053630:Depsides; D018696:Neuroprotective Agents; D014443:Tyrosine; D000097123:Rosmarinic Acid; C416518:clovamide