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

• DOI: 10.1021/acschemneuro.7b00527
• Publication Date: 2018-04-02T22:40:56Z
• Authors: Jialing Wang; Jiachen Zheng; Chunhui Huang; Jiaying Zhao; Jiajia Lin; Xuezhen Zhou; C. Benjamin Naman; Ning Wang; William H. Gerwick; Qinwen Wang; Xiaojun Yan; Wei Cui; Shan He
• Keywords: Neurons; 0301 basic medicine; Amyloid beta-Peptides; Glycogen Synthase Kinase 3 beta; Cell Survival; Peptide Fragments; 3. Good health; Neuroblastoma; 03 medical and health sciences; Neuroprotective Agents; Alzheimer Disease; Cell Line, Tumor; Nerve Degeneration; Humans

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.