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

Hye Ju Han,Ho Jin Heo,Jin Yong Kang,Jong Min Kim,Seul Ki Yoo,Dae-Ok Kim,Gun-Hee Kim,Seon Kyeong Park

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.

Highlights

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease, and is characterized by cognitive decline [1,2]
Behavioral Tests the Aβ injection had no effect on motor ability
The expression level of caspase-3 was 3 was inhibited by the administration of the mixture (P4F6), and these results demoninhibited by the administration of the mixture (P4F6), and these results demonstrated strated that the mixture (P4F6) was effective material for mitochondrial activation through that the mixture (P4F6) was effective material for mitochondrial activation through the the down-regulating of mitochondria-mediated apoptosis molecules

Summary

Introduction

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease, and is characterized by cognitive decline [1,2]. Amyloid-beta (Aβ) is a critical factor involved in AD, namely, senile plaques and cerebral amyloid angiopathy [1]. Cognitive dysfunction is related to complex mechanisms (neuroinflammation, cholinergic system, amyloid plaque, nerve growth factor) [2]. At the center of the complex cognitive dysfunction-related signaling mechanism, the Aβ peptides play a central role [1]. Aβ peptide, which is generated by the enzymatic cleavage of APP by β-secretase and Y-secretase, is known as a neurotoxin. The formation of Aβ oligomers in synaptic terminals is correlated with cognitive dysfunction through neurotransmission inhibition and cell death [3,4,5]

Methods

Discussion

Conclusion