Ethyl ferulate, a lipophilic polyphenol, induces HO-1 and protects rat neurons against oxidative stress

Giovanni Scapagnini, D. Allan Butterfield, Claudia Colombrita, Rukhsana Sultana, Alessia Pascale, Vittorio Calabrese

Research output: Contribution to journalReview articlepeer-review

164 Scopus citations


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 μM EFE in astrocytes and 5 μM EFE in neurons. Higher concentrations of EFE (50 μM) 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 resistence 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 neurode-generative conditions.

Original languageEnglish
Pages (from-to)811-818
Number of pages8
JournalAntioxidants and Redox Signaling
Issue number5
StatePublished - Oct 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Physiology
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology


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