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ACS Chem Neurosci. 2018 Jun 20;9(6):1349-1356. doi: 10.1021/acschemneuro.7b00527. Epub 2018 Apr 10.

Eckmaxol, a Phlorotannin Extracted from Ecklonia maxima, Produces Anti-β-amyloid Oligomer Neuroprotective Effects Possibly via Directly Acting on Glycogen Synthase Kinase 3β.

Author information

1
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center , Ningbo University , Ningbo 315211 , China.
2
Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine , Ningbo University , Ningbo 315211 , China.
3
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego , La Jolla , California 92093 , United States.
4
Department of Chemistry , Tsinghua University , Beijing 100084 , China.

Abstract

Alzheimer's disease is a progressive neurodegenerative disorder that mainly affects the elderly. Soluble β-amyloid oligomer, which can induce neurotoxicity, is generally regarded as the main neurotoxin in Alzheimer's disease. Here we report that eckmaxol, a phlorotannin extracted from the brown alga Ecklonia maxima, could produce neuroprotective effects in SH-SY5Y cells. Eckmaxol effectively prevented but did not rescue β-amyloid oligomer-induced neuronal apoptosis and increase of intracellular reactive oxygen species. Eckmaxol also significantly reversed the decreased expression of phospho-Ser9-glycogen synthase kinase 3β and increased expression of phospho-extracellular signal-regulated kinase, which was induced by Aβ oligomer. Moreover, both glycogen synthase kinase 3β and mitogen activated protein kinase inhibitors produced neuroprotective effects in SH-SY5Y cells. Furthermore, eckmaxol showed favorable interaction in the ATP binding site of glycogen synthase kinase 3β and mitogen activated protein kinase. These results suggested that eckmaxol might produce neuroprotective effects via concurrent inhibition of glycogen synthase kinase 3β and extracellular signal-regulated kinase pathways, possibly via directly acting on glycogen synthase kinase 3β and mitogen activated protein kinase. Based on the central role that β-amyloid oligomers play in the pathogenesis of Alzheimer's disease and the high annual production of Ecklonia maxima for alginate and other nutritional ingredients, this report represents a new candidate for the treatment of Alzheimer's disease, and also expands the potential application of Ecklonia maxima and its constituents in the field of pharmacology.

KEYWORDS:

Alzheimer’s disease; Eckmaxol; neuroprotection; oxidative stress; β-amyloid oligomer

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