title: Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells.
abstract: Beta-amyloid (Abeta) peptide, the hallmark of Alzheimer's disease (AD), invokes a cascade of oxidative damages to neurons and eventually leads to neuronal death. In this study, salidroside (Sald), an active compound isolated from a traditional Chinese medicinal plant, Rhodiola rosea L., was investigated to assess its protective effects and the underlying mechanisms against Abeta-induced oxidative stress in SH-SY5Y human neuroblastoma cells. Abeta(25-35)-induced neuronal toxicity was characterized by the decrease of cell viability, the release of lactate dehydrogenase (LDH), morphological alterations, neuronal DNA condensation, and the cleavage of poly(ADP-ribose) polymerase (PARP) by activated caspase-3. Pretreatment with salidroside markedly attenuated Abeta(25-35)-induced loss of cell viability and apoptosis in a dose-dependent manner. The mechanisms of salidroside protected neurons from oxidative stress included the induction of antioxidant enzymes, thioredoxin (Trx), heme oxygenase-1 (HO-1), and peroxiredoxin-I (PrxI); the downregulation of pro-apoptotic protein Bax and the upregulation of anti-apoptotic protein Bcl-X(L). Furthermore, salidroside dose-dependently restored Abeta(25-35)-induced loss of mitochondrial membrane potential (MMP) as well as suppressed the elevation of intracellular reactive oxygen species (ROS) level. It was also observed that Abeta(25-35) stimulated the phosphorylation of mitogen-activated protein (MAP) kinases, including c-Jun NH(2)-terminal kinase (JNK) and p38 MAP kinase, but not extracellular signal-regulated kinase1/2 (ERK1/2). Salidroside inhibited Abeta(25-35)-induced phosphorylation of JNK and p38 MAP kinase, but not ERK1/2. These results suggest that salidroside has protective effects against Abeta(25-35)-induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.
authors.affiliation: Jiangsu Institute of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health, Wuxi, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Huixin
authors.initials: H
authors.lastname: Yu
authors.forename: Xincan
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Lin
authors.forename: Chen
authors.initials: C
authors.lastname: Tan
authors.forename: Guoxian
authors.initials: G
authors.lastname: Cao
authors.forename: Zhengwu
authors.initials: Z
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D005434:Flow Cytometry; D005960:Glucosides / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012844:Sincalide / Q000378:metabolism; D014343:Trypan Blue; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017931:DNA Primers; D005960:Glucosides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010636:Phenols; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; D014343:Trypan Blue; D012844:Sincalide; C009172:rhodioloside