Bromoalkaloids protect primary cortical neurons from induced oxidative stress.
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.
Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela , Lugo 27003, Spain.
M
M
Leirós
E
E
Alonso
M E
ME
Rateb
W E
WE
Houssen
R
R
Ebel
M
M
Jaspars
A
A
Alfonso
L M
LM
Botana
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D061745:Antioxidant Response Elements / Q000502:physiology; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D000470:Alkaloids; D001381:Azepines; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D011758:Pyrroles; D012717:Sesquiterpenes; C107079:hymenialdisine; C022097:parthenin
Bromoalkaloids; Nrf2; cortical neurons; neuroprotection; oxidative stress; sponges