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

Abstract

Beta-amyloid (A beta) 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 A beta-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 microM A beta((1-42)) for 24 h caused morphologically cytotoxic changes, decreased cell viability and increased ROS level, whereas preincubation with 50-400 microg/mL ME 30 min before the induction by A beta((1-42)) successfully prevented such cytotoxic effects in a dose-dependent manner (completely at 400 microg/mL). The A beta-induced increase in caspase-3 activity was also preventable by 400 microg/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 A beta((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 A beta-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.

Korean Red Ginseng Extract Exhibits Neuroprotective Effects through Inhibition of Apoptotic Cell Death

“…4B, exposure of cells to A β (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) increased intracellular ROS levels, which was significantly inhibited by the co-treatment with KRG extract at 0.3 and 1 mg/mL. In contrast, memantine had no effect on the A β (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) -induced injury or ROS at the concentration tested (data not shown).…”

“…To investigate effects of KRG extract on the neuronal damage induced by glutamate, NMDA or A β (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) , the cells were simultaneously treated with various concentrations of KRG extract in combination with the respective insults as mentioned above. Following the desired treatments, the viability of cells was assessed as described below.…”

“…26,27) Briefly, cells were incubated with 10 µM DCFH-DA for 30 min at 37°C to allow the diffusion of the fluorescent probe into the cells and its subsequent hydrolysis to non-fluorescent dichlorofluorescin (DCFH) under the action of intracellular esterases. After removal of excess DCFH-DA, cells were washed with HCSS and then exposed to either L-glutamate or NMDA for 2 h at 37°C in the presence or absence of various concentrations of KRG extract.…”

“…The cells were then washed with HCSS and maintained in MEM for 22-24 h in the incubator. To induce neurotoxicity by A β , cells were exposed to aggregated A β (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) at a final concentration of 40 µM in MEM for 24 h at 37°C. 24) The control cells were treated with MEM without any agent.…”

The Pivotal Neuroinflammatory, Therapeutic and Neuroprotective Role of Alpha-Mangostin

“…On the other hand, α-MG has proven to mitigate the neurotoxicity triggered by beta-amyloid oligomers in SK-N-SH neuroblastoma cells and prime rat cerebral cortical neurons [57,83,96]. Studies [83,97] have further demonstrated that the antioxidative feature of α-MG is perhaps interceded by its regulatory influence on the movement of glutathione peroxidase.…”