Neuroprotective activity of macroalgal fucofuroeckols against amyloid β peptide-induced cell death and oxidative stress

Phlorotannins are polyphenolic compounds predominantly found in brown seaweeds tentatively identified as having neuroprotective bioactivity; however, the effects of individual constituent phlorotannins against amyloid β neurotoxicity, the main hallmark neurotoxic protein in Alzheimer’s disease (AD), is yet to be fully characterised. In this study, four phlorotannins, namely eckol, dieckol, phlorofucofuroeckol-A (PFFA) and 974-A sourced from the brown seaweed Ecklonia species were assessed for their ability to protect against the toxic effects of H₂O₂, lipid peroxidation via tert-butyl hydroperoxide (t-BHP) and Aβ_1–42 in neuronal PC12 cells. All compounds significantly scavenged reactive oxygen species (ROS). However, only PFFA and 974-A protected PC12 cells from oxidative stress-evoked neurotoxicity, providing significant increases in cell viability in response to both cytosolic (H₂O₂₎ and lipid peroxidation-evoked (t-BHP) cell stress. None of the phlorotannins tested inhibited Aβ_1–42 aggregate morphology, which suggested that their neuroprotective activity was unrelated to direct interactions with Aβ_1–42 protein. Our results indicate that while all phlorotannins tested exhibited ROS scavenging activity, only fucofuroeckol-type phlorotannins such as PFFA and 974-A afforded broader neuroprotective activity in response to both oxidative stress and amyloid β exposure. The additional amyloid-protective capacity of fucofuroeckols reveals the potential importance of the benzofuran moiety in neuroprotection and further studies are encouraged to investigate the chemico-biological basis of this distinction in the search for neuroprotective therapies in dementia and other neurodegenerative conditions.