β-
Amyloid (Aβ)-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 Aβ
intracerebroventricular infusion in mice. In this study, we investigated the effect of
xanthoceraside on the neurotoxicity of Aβ25-35 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 Aβ25-35 in a dose-dependent manner. Aβ25-35-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.