Accumulation and oligomerization of amyloid-beta (Aβ) peptides have been known to be a potent cause of neurodegenerative diseases such as Alzheimer's disease (AD). To expand the possibilities of preventing AD, we investigated the effects of resveratrol dimers, gnetin C and ε-viniferin, on Aβ 1-42 (Aβ42) production and the reduced cell viability observed after Aβ42 treatment (monomers, 10 μM) in cultured SH-SY5Y human neuroblastoma cells. Among them, addition of gnetin C (20 μM) into the media reduced Aβ42 production most efficiently. Gnetin C suppressed the expression of β-site amyloid precursor protein-cleaving enzyme-1 (BACE1, β-secretase). Furthermore, gnetin C ameliorated the Aβ42-reduced cell viability most significantly. Concomitantly, gnetin C reduced intracellular Aβ oligomers (ca. 15 and 130 kDa) and elevated both levels of intracellular and extracellular Aβ monomers. Under the treatment with or without Aβ42, gnetin C upregulated the expression of matrix metalloproteinase-14 (MMP-14) which is assumed to be an Aβ-decomposing enzyme. Gnetin C may thereby prevent Aβ toxicity by suppressing BACE1 and enhancing MMP-14, together with reducing both internalization and oligomerization of exogenous Aβ monomers. The use of gnetin C may lead to the prevention of Aβ-mediated diseases, particularly AD.

中文翻译：

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Gnetin C是一种白藜芦醇二聚体，可降低培养的SH-SY5Y人成神经细胞瘤细胞中淀粉样蛋白β1-42（Aβ42）的产生并改善Aβ42降低的细胞活力。

已知淀粉样β（Aβ）肽的积累和低聚是神经退行性疾病（例如阿尔茨海默氏病（AD））的有效原因。为了扩大预防AD的可能性，我们研究了白藜芦醇二聚体，netnetin C和ε-viniferin对培养的SH中Aβ1-42（Aβ42）产生和Aβ42处理（单体，10μM）后观察到的细胞活力降低的影响。 -SY5Y人神经母细胞瘤细胞。其中，向培养基中添加Gnetin C（20μM）最有效地降低了Aβ42的产生。Gnetin C抑制β位淀粉样蛋白前体蛋白裂解酶1（BACE1，β-分泌酶）的表达。此外，促胃泌素蛋白C最明显地改善了Aβ42降低的细胞活力。随之而来的是，Gnetin C还原了细胞内Aβ低聚物（ca. 15和130 kDa），并同时提高了细胞内和细胞外Aβ单体的水平。在有或没有Aβ42的处理下，促胃泌素C上调了被认为是Aβ分解酶的基质金属蛋白酶-14（MMP-14）的表达。netnetin C可以通过抑制BACE1和增强MMP-14来防止Aβ毒性，同时减少外源性Aβ单体的内在化和低聚化。胃泌素C的使用可以导致预防Aβ介导的疾病，特别是AD。以及减少外源性Aβ单体的内在化和低聚化。胃泌素C的使用可以导致预防Aβ介导的疾病，特别是AD。以及减少外源性Aβ单体的内在化和低聚化。胃泌素C的使用可以导致预防Aβ介导的疾病，特别是AD。