Protective effect of xanthoceraside against ß-amyloid-induced neurotoxicity in neuroblastoma SH-SY5Y cells.

ABSTRACT

ß-Amyloid (Aß)-induced neurotoxicity is a major pathological mechanism of Alzheimer's disease (AD). Xanthoceraside, a triterpene extracted from the husk of Xanthoceras sorbifolia Bunge, has been shown to have therapeutic effects on learning and memory impairment induced by Aß intracerebroventricular infusion in mice. In this study, we investigated the effect of xanthoceraside on the neurotoxicity of Aß25-35 in SH-SY5Y cells. Cell viability was measured by MTT (3-(3,4-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Cell apoptosis, reactive oxygen species (ROS) generation, and mitochondrion membrane potential (MMP) were measured using Annexin V/propidium iodide, 2,7-dichlorofluorescein diacetate, and rhodamine 123 with flow cytometry, respectively. Intracellular calcium level was determined with Fura-2/AM. Caspase-3 activity in cell lysates was measured using the spectrophotometric method. Results indicated that pretreatment with xanthoceraside (0.01 and 0.1 µM) obviously increased the viability of SH-SY5Y cells injured by Aß25-35 in a dose-dependent manner. Aß25-35-induced early apoptosis, ROS overproduction, MMP dissipation, intracellular calcium overload, and increase in caspase-3 activity were markedly reversed by xanthoceraside. These findings suggested that xanthoceraside might be useful in the prevention and treatment of AD.