Gnetin C, a resveratrol dimer, reduces amyloid-ß 1-42 (Aß42) production and ameliorates Aß42-lowered cell viability in cultured SH-SY5Y human neuroblastoma cells.

Accumulation and oligomerization of amyloid-beta (Aß) 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 Aß 1-42 (Aß42) production and the reduced cell viability observed after Aß42 treatment (monomers, 10 µM) in cultured SH-SY5Y human neuroblastoma cells. Among them, addition of gnetin C (20 µM) into the media reduced Aß42 production most efficiently. Gnetin C suppressed the expression of ß-site amyloid precursor protein-cleaving enzyme-1 (BACE1, ß-secretase). Furthermore, gnetin C ameliorated the Aß42-reduced cell viability most significantly. Concomitantly, gnetin C reduced intracellular Aß oligomers (ca. 15 and 130 kDa) and elevated both levels of intracellular and extracellular Aß monomers. Under the treatment with or without Aß42, gnetin C upregulated the expression of matrix metalloproteinase-14 (MMP-14) which is assumed to be an Aß-decomposing enzyme. Gnetin C may thereby prevent Aß toxicity by suppressing BACE1 and enhancing MMP-14, together with reducing both internalization and oligomerization of exogenous Aß monomers. The use of gnetin C may lead to the prevention of Aß-mediated diseases, particularly AD.