Spongionella secondary metabolites protect mitochondrial function in cortical neurons against oxidative stress.
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.
Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27003, Spain. marta.leiros@usc.es.
Marta
M
Leirós
Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27003, Spain. jonandoni.sanchez@rai.usc.es.
Jon A
JA
Sánchez
Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27003, Spain. eva.alonso@usc.es.
Eva
E
Alonso
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, Scotland AB24 3UE, UK. mostafa19772002@yahoo.com.
Mostafa E
ME
Rateb
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, Scotland AB24 3UE, UK. w.houssen@abdn.ac.uk.
Wael E
WE
Houssen
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, Scotland AB24 3UE, UK. r.ebel@abdn.ac.uk.
Rainer
R
Ebel
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, Scotland AB24 3UE, UK. m.jaspars@abdn.ac.uk.
Marcel
M
Jaspars
Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27003, Spain. amparo.alfonso@usc.es.
Amparo
A
Alfonso
Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27003, Spain. Luis.Botana@usc.es.
Luis M
LM
Botana
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011161:Porifera / Q000378:metabolism*
D004224:Diterpenes; D018696:Neuroprotective Agents; D006861:Hydrogen Peroxide