Bromoalkaloids protect primary cortical neurons from induced oxidative stress

Marta Leirós, Eva Alonso, Mostafa Rateb, Rainer Ebel, Marcel Jaspars, Amparo Alfonso, L.M. Botana

Research output: Contribution to journalArticle

9 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
JournalACS Chemical Neuroscience
Volume6
Issue number2
DOIs
Publication statusPublished - 18 Feb 2015
Externally publishedYes

Fingerprint

Oxidative stress
Neurons
Oxidative Stress
Metabolites
Antioxidants
Antioxidant Response Elements
Neurodegenerative diseases
Biomarkers
Neurodegenerative Diseases
Hydrogen Peroxide
Phosphotransferases
Cytokines
Oxidation
hymenialdisine
Research
Pharmaceutical Preparations
parthenin
Therapeutics

Cite this

Leirós, M., Alonso, E., Rateb, M., Ebel, R., Jaspars, M., Alfonso, A., & Botana, L. M. (2015). Bromoalkaloids protect primary cortical neurons from induced oxidative stress. ACS Chemical Neuroscience, 6(2), 331-338. https://doi.org/10.1021/cn500258c
Leirós, Marta ; Alonso, Eva ; Rateb, Mostafa ; Ebel, Rainer ; Jaspars, Marcel ; Alfonso, Amparo ; Botana, L.M. / Bromoalkaloids protect primary cortical neurons from induced oxidative stress. In: ACS Chemical Neuroscience. 2015 ; Vol. 6, No. 2. pp. 331-338.
@article{d0cd555c8c2b47f1be80136ad32fff35,
title = "Bromoalkaloids protect primary cortical neurons from induced oxidative stress",
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.",
author = "Marta Leir{\'o}s and Eva Alonso and Mostafa Rateb and Rainer Ebel and Marcel Jaspars and Amparo Alfonso and L.M. Botana",
year = "2015",
month = "2",
day = "18",
doi = "10.1021/cn500258c",
language = "English",
volume = "6",
pages = "331--338",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "2",

}

Leirós, M, Alonso, E, Rateb, M, Ebel, R, Jaspars, M, Alfonso, A & Botana, LM 2015, 'Bromoalkaloids protect primary cortical neurons from induced oxidative stress', ACS Chemical Neuroscience, vol. 6, no. 2, pp. 331-338. https://doi.org/10.1021/cn500258c

Bromoalkaloids protect primary cortical neurons from induced oxidative stress. / Leirós, Marta; Alonso, Eva; Rateb, Mostafa; Ebel, Rainer; Jaspars, Marcel; Alfonso, Amparo; Botana, L.M.

In: ACS Chemical Neuroscience, Vol. 6, No. 2, 18.02.2015, p. 331-338.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bromoalkaloids protect primary cortical neurons from induced oxidative stress

AU - Leirós, Marta

AU - Alonso, Eva

AU - Rateb, Mostafa

AU - Ebel, Rainer

AU - Jaspars, Marcel

AU - Alfonso, Amparo

AU - Botana, L.M.

PY - 2015/2/18

Y1 - 2015/2/18

N2 - 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.

AB - 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.

U2 - 10.1021/cn500258c

DO - 10.1021/cn500258c

M3 - Article

VL - 6

SP - 331

EP - 338

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 2

ER -