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PO2-1-59

Ecklonia radiata-derived phlorotannin extract inhibits beta-amyloid fibril formation and neurotoxicity

[Speaker] Scott D Smid:1
[Co-author] Dylan Whan:1, Wei Zhang:2, Masaya Fujitani:3, Ryuji Kato:3
1:Discipline of Pharmacology, The University of Adelaide, Australia, 2:Centre for Marine Bioproducts Development, Flinders University, Australia, 3:Laboratory of Cell and Molecular Bioengineering, Graduate School of Pharmaceutical Sciences, Nagoya University, Japan

Alzheimer's disease (AD) is a progressive and chronic neurodegenerative disease characterized by the presence of Beta-Amyloid Protein (Abeta) aggregates in the brain. Macroalgal-derived phlorotannins (PT) are polyphenolic compounds that resemble plant flavonoids known to be neuroprotective in Alzheimer's disease models. In this study we characterized the anti-aggregatory and neuroprotective effects of a phlorotannin extract from Ecklonia radiata against amyloid-beta (Abeta) aggregation and neurotoxicity. E. radiata was sourced fresh from regional coastal wrack (Rivoli Bay, South Australia), where crude PT extract was produced via solid-liquid extraction and liquid-liquid fractionation to reach a purity of 87% by biomass dry weight. Abeta anti-aggregatory effects of PT extract were subsequently evaluated using the thioflavin T assay of Abeta kinetics and transmission electron microscopy (TEM) to directly visualise Abeta fibrils. Neuroprotection was assessed in neuronal PC12 cells exposed to Abeta1-42 for 48 hrs in the presence of PT extract (0-100 microg/ml) and in mouse cortical neural stem cells (mNSCs) exposed to extract alone to assess its intrinsic properties. The PT extract demonstrated significant anti-aggregative properties, inhibiting fibril formation at 50 and 100 microg/ml (P<0.05) and inhibiting Abeta-induced toxicity in PC12 cells from 10 microg/ml. At <10 microg/ml, PT extract elicited differentiation of mNSCs, but at higher concentrations (>40 microg/ml), Ecklonia extract was neurotoxic in mNSCs. Further refinement and analysis of the extract revealed a novel constituent phlorotannin that may aid in the development of novel therapeutic treatments in Alzheimer's disease.
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