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

Abstract

Summary 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 Aβ1–42 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 Aβ1–42 aggregate morphology, which suggested that their neuroprotective activity was unrelated to direct interactions with Aβ1–42 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.

Marine Macroalgae Polyphenols as Potential Neuroprotective Antioxidants in Neurodegenerative Diseases

“…Specifically, the two fucofuroeckols (PFFA and 974-A) were found to significantly protect PC12 cells exposed to 150 and 200 µM of t-BHP, whereas eckol and dieckol did not offer any protection. Intriguingly, all the tested phlorotannins were found to effectively scavenge intracellular ROS, which is likely related to their phenol rings acting as electron traps to scavenge peroxynitrite, superoxide anions, and hydroxyl radicals, as previously noted by the authors [92].…”

“…In the study of Shrestha et al [ 92 ], four phlorotannins, namely eckol, dieckol, phlorofucofuroeckol-A (PFFA), and 974-A sourced from the brown seaweed Ecklonia species were tested to evaluate their neuroprotective action. Aβ42, H 2 O 2 , and the lipid peroxidant tert-butyl hydroperoxide (t-BHP) were used to induce oxidative stress and toxicity in neuronal PC12 cells.…”

“…None of the phlorotannins tested inhibited Aβ42 aggregate morphology, which suggested that their neuroprotective activity was unrelated to direct interactions with Aβ42 proteins. Our results indicate that although all phlorotannins tested exhibited ROS scavenging activity, only phlorotannins PFFA and 974-A afforded broader neuroprotective activity in response to both oxidative stress and amyloid beta exposure [ 92 ].…”

“…These findings emphasize the potential of a class of phlorotannins from brown seaweed called fucofuroeckols, which can successfully reduce oxidative stress and Aβ-evoked toxicity relevant to neurodegenerative pathways in AD. Additional in vivo studies to further establish preclinical efficacy as a guide to guiding further clinical trials in nutraceutical or pharmaceutical settings are needed in the future, as are studies to differentiate the mechanistic basis for the protection provided by fucofuroeckols [ 92 ].…”

From the ocean to the brain: harnessing the power of marine algae for neuroprotection and therapeutic advances

“…Another group of seaweed compounds with potential neuroprotective effects is the phlorotannins. These polyphenolic compounds have been shown to have antioxidant and anti-inflammatory properties, as well as the ability to inhibit the formation of β-amyloid plaques, which are a hallmark of AD [17,18].…”