Protective effect of mangosteen extract against beta-amyloid-induced cytotoxicity, oxidative stress and altered proteome in SK-N-SH cells.
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.
Moongkarndi
Primchanien
P
Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Srisawat
Chatchawan
C
Saetun
Putita
P
Jantaravinid
Jiraporn
J
Peerapittayamongkol
Chayanon
C
Soi-ampornkul
Rungtip
R
Junnu
Sarawut
S
Sinchaikul
Supachok
S
Chen
Shui-Tein
ST
Charoensilp
Patcharakajee
P
Thongboonkerd
Visith
V
Neungton
Neelobol
N
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000704:Analysis of Variance; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D029762:Garcinia mangostana / Q000737:chemistry*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D020543:Proteome / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric; D028961:beta Karyopherins / Q000378:metabolism
D016229:Amyloid beta-Peptides; C424166:KPNB1 protein, human; D018696:Neuroprotective Agents; D010936:Plant Extracts; D020543:Proteome; D017382:Reactive Oxygen Species; D028961:beta Karyopherins; D053148:Caspase 3