Fucoidan-Rich Substances from Ecklonia cava Improve Trimethyltin-Induced Cognitive Dysfunction via Down-Regulation of Amyloid β Production/Tau Hyperphosphorylation

Mar Drugs. 2019 Oct 17;17(10):591. doi: 10.3390/md17100591.

Abstract

Ecklonia cava (E. cava) was investigated to compare the effect of polyphenol and fucoidan extract and mixture (polyphenol:fucoidan = 4:6) on cognitive function. The ameliorating effect of E. cava was evaluated using the Y-maze, passive avoidance and Morris water maze tests with a trimethyltin (TMT)-induced cognitive dysfunction model, and the results showed that the fucoidan extract and mixture (4:6) had relatively higher learning and memory function effects than the polyphenol extract. After a behavioral test, the inhibitory effect of lipid peroxidation and cholinergic system activity were examined in mouse brain tissue, and the fucoidan extract and mixture (4:6) also showed greater improvements than the polyphenol extract. Mitochondrial activity was evaluated using mitochondrial reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP, ΔΨm), adenosine triphosphate (ATP) content, and mitochondria-mediated protein (BAX, cytochrome C) analysis, and these results were similar to the results of the behavioral tests. Finally, to confirm the cognitive function-related mechanism of E. cava, the amyloid-β production and tau hyperphosphorylation-medicated proteins were analyzed. Based on these results, the improvement effect of E. cava was more influenced by fucoidan than polyphenol. Therefore, our study suggests that the fucoidan-rich substances in E. cava could be a potential material for improving cognitive function by down-regulating amyloid-β production and tau hyperphosphorylation.

Keywords: Ecklonia cava; amyloid beta; cognitive function; tau; trimethyltin.

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Down-Regulation / drug effects*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Memory / drug effects
  • Mice
  • Mice, Inbred ICR
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Peptide Fragments / pharmacology
  • Phaeophyta / chemistry*
  • Phosphorylation / drug effects*
  • Polysaccharides / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Trimethyltin Compounds / pharmacology
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • Polysaccharides
  • Reactive Oxygen Species
  • Trimethyltin Compounds
  • tau Proteins
  • trimethyltin
  • fucoidan