Protective Effect of Mangosteen Extract against β-Amyloid-Induced Cytotoxicity, Oxidative Stress and Altered Proteome in SK-N-SH Cells

Abstract

β-amyloid (Aβ) plays a key role in the pathogenesis of Alzheimer’s disease (AD) by inducing neurotoxicity and cell death mainly through production of reactive oxygen species (ROS). Garcinia mangostana L. (mangosteen) has been recognized as a major source of natural antioxidants that could decrease ROS. However, its role in protection of Aβ-induced cytotoxicity and apoptosis in neuronal cells remains unclear. We therefore examined such a protective effect of mangosteen extract (ME) by evaluating cell viability using MTT test, ROS level, caspase-3 activity, and cellular proteome. Treating SK-N-SH cells with 5−20 μM Aβ₍₁₋₄₂₎ for 24 h caused morphologically cytotoxic changes, decreased cell viability and increased ROS level, whereas preincubation with 50−400 μg/mL ME 30 min before the induction by Aβ₍₁₋₄₂₎ successfully prevented such cytotoxic effects in a dose-dependent manner (completely at 400 μg/mL). The Aβ-induced increase in caspase-3 activity was also preventable by 400 μg/mL ME. Proteomic analysis using 2-D gel electrophoresis (n = 5 gels/group) followed by mass spectrometry revealed 63 proteins whose levels were significantly altered by Aβ₍₁₋₄₂₎ induction. Interestingly, changes in 10 proteins were successfully prevented by the ME pretreatment. In summary, we report herein the significant protective effects of ME against Aβ-induced cytotoxicity, increased ROS, and increased caspase activity in SK-N-SH cells. Moreover, proteomic analysis revealed some proteins that might be responsible for these protective effects by ME. Further characterizations of these proteins may lead to identification of novel therapeutic targets for successful prevention and/or decreasing the severity of AD.