Spongionella secondary metabolites protect mitochondrial function in cortical neurons against oxidative stress

Marta Leirós, Jon A Sánchez, Eva Alonso, Mostafa E Rateb, Wael E Houssen, Rainer Ebel, Marcel Jaspars, Amparo Alfonso, Luis M Botana, Mostafa Ezzat Mohamed Rateb

Research output: Contribution to journalArticle

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Abstract

The marine habitat provides a large number of structurally-diverse bioactive compounds for drug development. Marine sponges have been studied over many years and are found to be a rich source of these bioactive chemicals. This study is focused on the evaluation of the activity of six diterpene derivatives isolated from Spongionella sp. on mitochondrial function using an oxidative in vitro stress model. The test compounds include the Gracilins (A, H, K, J and L) and tetrahydroaplysulphurin-1. Compounds were co-incubated with hydrogen peroxide for 12 hours to determine their protective capacities and their effect on markers of apoptosis and Nrf2/ARE pathways was evaluated. Results conclude that Gracilins preserve neurons against oxidative damage, and that in particular, tetrahydroaplysulphurin-1 shows a complete neuroprotective activity. Oxidative stress is linked to mitochondrial dysfunction and consequently to neurodegenerative disorders like Parkinson and Alzheimer diseases, Friedreich ataxia or Amyotrophic lateral sclerosis. This neuroprotection against oxidation conditions suggest that these metabolites could be interesting lead candidates in drug development for neurodegenerative diseases.

Original languageEnglish
Pages (from-to)700-718
Number of pages19
JournalMarine Drugs
Volume12
Issue number2
Early online date27 Jan 2014
DOIs
Publication statusPublished - Feb 2014

Fingerprint

Neurodegenerative Diseases
Oxidative Stress
Friedreich Ataxia
Neurons
Diterpenes
Amyotrophic Lateral Sclerosis
Porifera
Pharmaceutical Preparations
Hydrogen Peroxide
Ecosystem
Parkinson Disease
Alzheimer Disease
Apoptosis
In Vitro Techniques
Neuroprotection

Keywords

  • diterpenes
  • Porifera
  • mitochondrial function
  • oxidative stress
  • neurodegenerative disorders

Cite this

Spongionella secondary metabolites protect mitochondrial function in cortical neurons against oxidative stress. / Leirós, Marta; Sánchez, Jon A; Alonso, Eva; Rateb, Mostafa E; Houssen, Wael E; Ebel, Rainer; Jaspars, Marcel; Alfonso, Amparo; Botana, Luis M; Rateb, Mostafa Ezzat Mohamed.

In: Marine Drugs, Vol. 12, No. 2, 02.2014, p. 700-718.

Research output: Contribution to journalArticle

Leirós, Marta ; Sánchez, Jon A ; Alonso, Eva ; Rateb, Mostafa E ; Houssen, Wael E ; Ebel, Rainer ; Jaspars, Marcel ; Alfonso, Amparo ; Botana, Luis M ; Rateb, Mostafa Ezzat Mohamed. / Spongionella secondary metabolites protect mitochondrial function in cortical neurons against oxidative stress. In: Marine Drugs. 2014 ; Vol. 12, No. 2. pp. 700-718.
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abstract = "The marine habitat provides a large number of structurally-diverse bioactive compounds for drug development. Marine sponges have been studied over many years and are found to be a rich source of these bioactive chemicals. This study is focused on the evaluation of the activity of six diterpene derivatives isolated from Spongionella sp. on mitochondrial function using an oxidative in vitro stress model. The test compounds include the Gracilins (A, H, K, J and L) and tetrahydroaplysulphurin-1. Compounds were co-incubated with hydrogen peroxide for 12 hours to determine their protective capacities and their effect on markers of apoptosis and Nrf2/ARE pathways was evaluated. Results conclude that Gracilins preserve neurons against oxidative damage, and that in particular, tetrahydroaplysulphurin-1 shows a complete neuroprotective activity. Oxidative stress is linked to mitochondrial dysfunction and consequently to neurodegenerative disorders like Parkinson and Alzheimer diseases, Friedreich ataxia or Amyotrophic lateral sclerosis. This neuroprotection against oxidation conditions suggest that these metabolites could be interesting lead candidates in drug development for neurodegenerative diseases.",
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AU - Alfonso, Amparo

AU - Botana, Luis M

AU - Rateb, Mostafa Ezzat Mohamed

N1 - Accepted: 8 January 2014 This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Acknowledgments The research leading to these results has received funding from the following FEDER cofunded-grants: From Ministerio de Ciencia y Tecnología, Spain: AGL2009-13581-CO2-01, AGL2012-40485-CO2-01. From Xunta de Galicia, Spain: 10PXIB261254 PR. From the European Union’s Seventh Framework Programme managed by REA—Research Executive Agency (FP7/2007–2013) under grant agreement Nos. 265896 BAMMBO, 265409 µAQUA, and 262649 BEADS, 315285 CIGUATOOLS and 312184 PHARMASEA. From the Atlantic Area Programme (Interreg IVB Trans-national): 2009-1/117 Pharmatlantic. MER thanks the Government of the Arab Republic of Egypt for a PhD Scholarship. MJ thanks the Scottish University Life Science Alliance which provided funding to set up the compound library.

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N2 - The marine habitat provides a large number of structurally-diverse bioactive compounds for drug development. Marine sponges have been studied over many years and are found to be a rich source of these bioactive chemicals. This study is focused on the evaluation of the activity of six diterpene derivatives isolated from Spongionella sp. on mitochondrial function using an oxidative in vitro stress model. The test compounds include the Gracilins (A, H, K, J and L) and tetrahydroaplysulphurin-1. Compounds were co-incubated with hydrogen peroxide for 12 hours to determine their protective capacities and their effect on markers of apoptosis and Nrf2/ARE pathways was evaluated. Results conclude that Gracilins preserve neurons against oxidative damage, and that in particular, tetrahydroaplysulphurin-1 shows a complete neuroprotective activity. Oxidative stress is linked to mitochondrial dysfunction and consequently to neurodegenerative disorders like Parkinson and Alzheimer diseases, Friedreich ataxia or Amyotrophic lateral sclerosis. This neuroprotection against oxidation conditions suggest that these metabolites could be interesting lead candidates in drug development for neurodegenerative diseases.

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