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

doi:10.1021/cn500258c

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 journal › Article › peer-review

15 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 language	English
Pages (from-to)	331-338
Number of pages	8
Journal	ACS Chemical Neuroscience
Volume	6
Issue number	2
Early online date	12 Nov 2014
DOIs	https://doi.org/10.1021/cn500258c
Publication status	Published - Feb 2015

Bibliographical note

Funding
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.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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.

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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.",

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",

author = "M. Leiros and E. Alonso and Rateb, {M. E.} and Houssen, {W. E.} and R. Ebel and M. Jaspars and A. Alfonso and Botana, {L. M.}",

note = "Funding 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{\textquoteright}s Seventh Framework Programme managed by REA−Research Executive Agency (FP7/2007-2013) under grant agreement nos. 265409 μAQUA, 315285 CIGUATOOLS, and 312184 PHARMASEA. Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS 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.",

year = "2015",

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doi = "10.1021/cn500258c",

language = "English",

volume = "6",

pages = "331--338",

journal = "ACS Chemical Neuroscience",

issn = "1948-7193",

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T1 - Bromoalkaloids Protect Primary Cortical Neurons from Induced Oxidative Stress

AU - Leiros, M.

AU - Alonso, E.

AU - Rateb, M. E.

AU - Houssen, W. E.

AU - Ebel, R.

AU - Jaspars, M.

AU - Alfonso, A.

AU - Botana, L. M.

N1 - Funding 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. Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS 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.

PY - 2015/2

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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.

KW - Bromoalkaloids

KW - cortical neurons

KW - neuroprotection

KW - Nrf2

KW - oxidative stress

KW - sponges

KW - neurodegenerative diseases

KW - bromopyrrole alkaloids

KW - Alzheimers-Disease

KW - natural-product

KW - prostaglandin E-2

KW - in-vitro

KW - A-beta

KW - marine

KW - hymenialdisine

KW - inhibition

U2 - 10.1021/cn500258c

DO - 10.1021/cn500258c

M3 - Article

SN - 1948-7193

VL - 6

SP - 331

EP - 338

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

IS - 2

ER -

Bromoalkaloids Protect Primary Cortical Neurons from Induced Oxidative Stress

Abstract

Bibliographical note

Keywords

UN SDGs

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