Neuroprotective effects of three flavonoids from Acer okamotoanum against neurotoxicity induced by amyloid beta in SH-SY5Y cells

Abstract

Amyloid beta (Aβ) is produced from an amyloid precursor protein by the activation of the amyloidogenic pathway, and it is widely known to cause Alzheimer’s disease (AD). In this study, we investigated the neuroprotective effects of three flavonoids, quercitrin, isoquercitrin, and afzelin, from Acer okamotoanum against Aβ-induced neurotoxicity in SHSY5Y neuronal cells. Aβ25-35 treatments resulted in decreased cell viability and increased levels of nuclei condensation and fragmentation. However, an isoquercitrin treatment dosedependently increased cell viability and decreased nuclei condensation and fragmentation levels. SH-SY5Y cells treated with Aβ25-35 showed increased reactive oxygen species (ROS) production compared to that from cells not treated with Aβ25-35. However, treatment with the three flavonoids significantly inhibited ROS production compared to an Aβ25-35-treated control group, indicating that the three flavonoids blocked neuronal oxidative stress. For a closer examination of the neuroprotective mechanisms, we measured the expressions of the non-amyloidogenic pathway-related proteins of a disintegrin and metalloprotease 10 (ADAM10) and the tumor necrosis factor-α converting enzyme (TACE). An isoquercitrin treatment enhanced the expressions of ADAM10 compared to the control group. In addition, the three flavonoids activated the non-amyloidogenic pathway via the upregulation of TACE. In conclusion, we demonstrated neuroprotective effects of three flavonoids from A. okamotoanum, in particular isoquercitrin, on neurotoxicity by the regulation of the nonamyloidogenic pathway in Aβ25-35-treated SH-SY5Y cells. Therefore, we suggest that flavonoids from A. okamotoanum may have some potential as therapeutics of AD.