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.

中文翻译：

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Eckmaxol，一种从最大的Ecklonia中提取的环戊宁，可能通过直接作用于糖原合酶激酶3β而产生抗β-淀粉样寡聚体的神经保护作用。

阿尔茨海默氏病是一种进行性神经退行性疾病，主要影响老年人。可以诱导神经毒性的可溶性β-淀粉样蛋白低聚物通常被认为是阿尔茨海默氏病的主要神经毒素。在这里我们报道eckmaxol，一种从褐藻Ecklonia maxima提取的邻苯二酚可以在SH-SY5Y细胞中产生神经保护作用。Eckmaxol有效预防但不能挽救β-淀粉样低聚物诱导的神经元凋亡和细胞内活性氧的增加。Eckmaxol还显着逆转了由Aβ寡聚物诱导的磷酸化Ser9糖原合酶激酶3β的减少表达和磷酸化细胞外信号调节激酶的增加。此外，糖原合酶激酶3β和有丝分裂原活化的蛋白激酶抑制剂在SH-SY5Y细胞中均产生神经保护作用。此外，eckmaxol在糖原合酶激酶3β和有丝分裂原活化蛋白激酶的ATP结合位点显示出良好的相互作用。这些结果表明，eckmaxol可能通过同时抑制糖原合酶激酶3β和细胞外信号调节激酶途径，可能通过直接作用于糖原合酶激酶3β和促分裂原活化蛋白激酶而产生神经保护作用。基于β淀粉样蛋白寡聚体在阿尔茨海默氏病的发病机理和高年产量中的重要作用最大海藻Ecklonia用于藻酸盐和其他营养成分，该报告代表了阿尔茨海默氏病治疗的新候选人，并且扩大了最大海藻Ecklonia及其成分在药理学领域的潜在应用。