Bromoalkaloids Protect Primary Cortical Neurons from Induced Oxidative Stress

M. Leiros, E. Alonso, M. E. Rateb, W. E. Houssen, R. Ebel, M. Jaspars, A. Alfonso, L. M. Botana*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Bromoalkaloids are secondary metabolites with a demonstrated high activity in several therapeutic areas. In this research, we probe the neuroprotective and antioxidant activities of hymenialdisine and hymenin. Both structures were tested in an oxidative stress cellular model, consisting of cortical neurons that are incubated with the oxidative stress inducer hydrogen peroxide and the tested compound. Several oxidation biomarkers were analyzed, and the results of the oxidative stress induced neurons in the presence and absence of bromoalkaloids were compared. Both compounds demonstrated significant neuroprotective ability under stress conditions at low nanomolar concentrations, with hymenialdisine highlighted for demonstrating a more complete protection. Also, the activity of hymenialdisine and hymenin was studied in the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, and, for the first time, these halogenated metabolites are described as Nrf2 inducers, reinforcing the antioxidant capacity observed and therefore opening a new path of investigation. These results, added to the previously described effect of this compound family in negatively modulating several kinases and proinflammatory cytokines, position hymenialdisine and hymenin as good candidates for the development of new drugs for neurodegenerative diseases.

Original languageEnglish
Pages (from-to)331-338
Number of pages8
JournalACS Chemical Neuroscience
Volume6
Issue number2
Early online date12 Nov 2014
DOIs
Publication statusPublished - Feb 2015

Keywords

  • Bromoalkaloids
  • cortical neurons
  • neuroprotection
  • Nrf2
  • oxidative stress
  • sponges
  • neurodegenerative diseases
  • bromopyrrole alkaloids
  • Alzheimers-Disease
  • natural-product
  • prostaglandin E-2
  • in-vitro
  • A-beta
  • marine
  • hymenialdisine
  • inhibition

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