title: Ethyl ferulate, a lipophilic polyphenol, induces HO-1 and protects rat neurons against oxidative stress.
abstract: In the CNS, the heme oxygenase (HO) system has been reported to be active and to operate as a fundamental defensive mechanism for neurons exposed to an oxidant challenge. We have recently shown that both curcumin and caffeic acid phenethyl ester, two phenolic natural compounds, potently induce HO-1 expression and activity in rat astrocytes. We have extended our previous findings examining the effects of two other plant-derived phenolic compounds, with analogous chemical structures, in rat astrocytes and neurons. Ethyl ferulate (ethyl 4-hydroxy-3-methoxycinnamate) (EFE), the naturally occurring ester of ferulic acid, was able to induce HO-1 protein expression. Maximal expression of HO-1 mRNA and protein and a significant increase in HO activity were detected after 6 h of incubation with 15 microM EFE in astrocytes and 5 microM EFE in neurons. Higher concentrations of EFE (50 microM) caused a substantial cytotoxic effect with no change in HO-1 protein expression and activity. Exposure of astrocytes to resveratrol, a phytoalexin derived from grapes, resulted in an increase of HO-1 mRNA, but it was not able to induce HO-1 protein expression and activity. Interestingly, preincubation (12 h) of neurons with EFE resulted in an enhanced cellular resistance to glucose oxidase-mediated oxidative damage; this cytoprotective effect was considerably attenuated by zinc protoporphyrin IX, an inhibitor of HO activity. This study identifies a novel natural compound that could be used for therapeutic purposes as a potent inducer of HO-1 for the protection of brain cells against oxidative and neurodegenerative conditions.
authors.affiliation: Institute of Neurological Sciences, CNR, 95123 Catania, Italy. gscapag@brni-jhu.edu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scapagnini
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
authors.forename: Claudia
authors.initials: C
authors.lastname: Colombrita
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Alessia
authors.initials: A
authors.lastname: Pascale
authors.forename: Vittorio
authors.initials: V
authors.lastname: Calabrese
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002109:Caffeic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival; D004790:Enzyme Induction; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D013267:Stilbenes; C099085:ethyl ferulate; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D000077185:Resveratrol