Eckmaxol, a phlorotannin extracted from ecklonia maxima, produces anti-ss-amyloid oligomer neuroprotective effects possibly via directly acting on glycogen synthase kinase 3 ss

TitleEckmaxol, a phlorotannin extracted from ecklonia maxima, produces anti-ss-amyloid oligomer neuroprotective effects possibly via directly acting on glycogen synthase kinase 3 ss
Publication TypeJournal Article
Year of Publication2018
AuthorsWang J.L, Zheng J.C, Huang C.H, Zhao J.Y, Lin JJ, Zhou X.Z, Naman C.B, Wang N., Gerwick WH, Wang Q.W, Yan X.J, Cui W., He S.
Volume9
Pagination1349-1356
Date Published2018/06
Type of ArticleArticle
ISBN Number1948-7193
Accession NumberWOS:000436211800017
Keywords& Neurology; Alzheimer's disease; alzheimers-disease; beta oligomers; Biochemistry & Molecular Biology; brown alga; cells; diagnosis; Eckmaxol; fucoxanthin; h2o2-induced oxidative stress; ht22; induced cognitive impairments; neuroprotection; Neurosciences; oxidative stress; Pharmacology & Pharmacy; responses; ss-amyloid oligomer
Abstract

Alzheimer's disease is a progressive neurodegenerative disorder that mainly affects the elderly. Soluble ss-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 ss-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 3 ss and increased expression of phospho-extracellular signal-regulated kinase, which was induced by A ss oligomer. Moreover, both glycogen synthase kinase 3 ss 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 3 ss and mitogen activated protein kinase. These results suggested that eckmaxol might produce neuroprotective effects via concurrent inhibition of glycogen synthase kinase 3 ss and extracellular signal-regulated kinase pathways, possibly via directly acting on glycogen synthase kinase 3 ss and mitogen activated protein kinase. Based on the central role that ss-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.

DOI10.1021/acschemneuro.7b00527
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