Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells

Beta-amyloid (A beta) 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 (Said), 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 A beta-induced oxidative stress in SH-SY5Y human neuroblastoma cells. A beta(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 A beta(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 antiapoptotic protein Bcl-X-L. Furthermore, salidroside dose-dependently restored A beta(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 A beta(25-35) stimulated the phosphorylation of mitogen-activated protein (MAP) kinases, including c-Jun NH2-terminal kinase (INK) and p38 MAP kinase, but not extracellular signal-regulated kinase 1/2 (ERK1/2). Salidroside inhibited A beta(25-35)-induced phosphorylation of JNK and p38 MAP kinase, but not ERK1/2. These results suggest that salidroside has protective effects against A beta(25-35)-induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases. (C) 2010 Elsevier Ltd. All rights reserved.