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 journalArticlepeer-review

15 Citations (Scopus)


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
Issue number2
Early online date12 Nov 2014
Publication statusPublished - Feb 2015

Bibliographical note

The research leading to these results has received funding from the following FEDER co-funded grants. From CDTI and Technological Funds, supported by Ministerio de Economia y ́
Competitividad, AGL2012-40185-CO2-01, and Conselleria de ́ Cultura, Educacion e Ordenacio ́ n Universitaria, GRC2013-016, ́ and through Axencia Galega de Innovacion, Spain, ITC- ́
20133020 SINTOX, IN852A 2013/16-3 MYTIGAL. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA−Research Executive Agency (FP7/2007-2013) under grant agreement nos. 265409 μAQUA, 315285 CIGUATOOLS, and 312184 PHARMASEA.
The authors declare no competing financial interest.
We acknowledge the contribution of the Institute of Applied Science at the University of the South Pacific in Suva, Fiji, for assistance in the collection of the sponge material. The Scottish
University Life Science Alliance is acknowledged for their funding of the Marine Biodiscovery Centre Compound Library.


  • 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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