Neuroprotective activity of macroalgal fucofuroeckols against amyloid beta 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 beta 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 A beta(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 peroxidationevoked (t-BHP) cell stress. None of the phlorotannins tested inhibited A beta(1-42) aggregate morphology, which suggested that their neuroprotective activity was unrelated to direct interactions with A beta(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 beta 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.

Automated summary

Phlorotannins exhibit neuroprotective activity against oxidative stress and amyloid beta exposure, with fucofuroeckol-type phlorotannins showing broader neuroprotective effects.