Effect of low-concentration amyloid-β 1–42 (Aβ42) on human neuroblastoma  SH-SY5Y cell viability: neuroprotective potential of combination use with carnosic acid, rebamipide, edaravone, and resveratrol

Yoshida Hidemi, Hashimoto Yuko, Fukushima Takashi, Tanji Kunikazu, Matsumiya Tomoh, Seya Kazuhiko, Kawaguchi Shogo, Imaizumi Tadaatsu

doi:10.32216/hirosakiigaku.70.1_24

Toxic amyloid-beta (Aβ) is known to generate symptoms of Alzheimer’s disease (AD); however, less is known regarding the neurotoxicity of Aβ at lower concentrations. Moreover, the neuroprotective potential of combination treatment with plant biophenols and existing drugs is not well understood. In this study, we estimated the no-observed adverse effect level (NOAEL) of Aβ 1–42 (Aβ42) against cultured human neuroblastoma SH-SY5Y cells, and examined the neuroprotective effect of combination pretreatment with 10 µM carnosic acid, 30 nM rebamipide, 10 µM edaravone, and 10 µM of resveratrol (the “CRER” blend) on weak but toxic Aβ42-treated SH-SY5Y cells. We evaluated the NOAEL of Aβ42 at 500 nM in these cells. Aβ42 at 1–8 µM reduced cell viability; however, the “CRER” blend ameliorated this Aβ42-induced decrease in viability. The “CRER” blend induced the expression of Aβ-degrading enzymes including matrix metalloproteinase-14 (MMP-14) and neprilysin, while also enhancing the expression of the inducible α-secretase TACE (tumor necrosis factor-α-converting enzyme), sirtuin 1 (SIRT1), and brain-derived neurotrophic factor (BDNF). Collectively, our results indicate that the “CRER” may aid in the prevention of Aβ toxicity by enhancing MMP-14, neprilysin, TACE, SIRT1, and BDNF. Thus, the “CRER” blend may prove to be a promising strategy for the prevention of Aβ-mediated disorders, particularly AD.

Effect of low-concentration amyloid-β 1–42 (Aβ42) on human neuroblastoma SH-SY5Y cell viability: neuroprotective potential of combination use with carnosic acid, rebamipide, edaravone, and resveratrol

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