Mixture of Phlorotannin and Fucoidan from Ecklonia cava Prevents the Aβ-Induced Cognitive Decline with Mitochondrial and Cholinergic Activation

Mar Drugs. 2021 Jul 29;19(8):434. doi: 10.3390/md19080434.

Abstract

The anti-amnesic effect of a mixture (4:6 = phlorotannin:fucoidan from Ecklonia cava, P4F6) was evaluated on amyloid-beta peptide (Aβ)-induced cognitive deficit mice. The cognitive function was examined by Y-maze, passive avoidance, and Morris water maze tests, and the intake of the mixture (P4F6) showed an ameliorating effect on Aβ-induced learning and memory impairment. After the behavioral tests, superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) contents were confirmed in brain tissue, and in the results, the mixture (P4F6) attenuated Aβ-induced oxidative stress. In addition, mitochondrial activity was evaluated by mitochondrial reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic signaling pathway, and the mixture (P4F6) enhanced mitochondrial function. Furthermore, the mixture (P4F6) effectively regulated tau hyperphosphorylation by regulating the protein kinase B (Akt) pathway, and promoted brain-derived neurotrophic factor (BDNF) in brain tissue. Moreover, in the cholinergic system, the mixture (P4F6) ameliorated acetylcholine (ACh) content by regulating acetylcholinesterase (AChE) activity and choline acetyltransferase (ChAT) expression in brain tissue. Based on these results, we suggest that this mixture of phlorotannin and fucoidan (P4F6) might be a substance for improving cognitive function by effectively regulating cognition-related molecules.

Keywords: Ecklonia cava; amyloid-beta; cholinergic function; cognition; fucoidan; mitochondrial function; phlorotannin; tau phosphorylation.

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Aquatic Organisms
  • Brain / drug effects
  • Brain / metabolism
  • Cholinergic Agents / metabolism
  • Cognitive Dysfunction / drug therapy*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Kelp*
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred ICR
  • Mitochondria / metabolism
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / pharmacology
  • Phytotherapy
  • Polysaccharides / administration & dosage*
  • Polysaccharides / pharmacology
  • Tannins / administration & dosage*
  • Tannins / pharmacology

Substances

  • Cholinergic Agents
  • Neuroprotective Agents
  • Polysaccharides
  • Tannins
  • fucoidan
  • Acetylcholine