acteoside and Nerve-Degeneration

Our previous study has shown that acteoside, an antioxidative phenylethanoid glycoside, protect against beta-amyloid (Aβ)-induced cytotoxicity in vitro. However, the precise protective mechanisms remains unclear. Heme oxygenase-1 (HO-1) is a crucial factor in the response to oxidative injury, protecting neurons against Aβ-induced injury. In the present study we examined to determine whether acteoside upregulates HO-1 expression, and thereby protects PC12 cells against Aβ-induced cell death. It was revealed that acteoside is an activator of Nrf2 and inducer of HO-1 expression. We showed that acteoside increased HO-1 expression in vitro and in vivo. Acteoside treatment resulted in nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2). Acteoside activated both ERK and PI3 K/Akt, and treatments with the specific ERK inhibitor PD98059, the PI3 K inhibitor LY294002, and the specific Nrf2 siRNA suppressed the acteoside-induced HO-1 expression. The HO-1 inhibitor ZnPP, PD98059, and LY294002 markedly abolished the neuroprotective effect of acteoside against Aβ-induced neurotoxicity. Taken together, these results demonstrate that acteoside is an activator of Nrf2 and inducer of HO-1 expression. We also showed that acteoside increased HO-1 expression through activation of ERK and PI3 K/Akt signal pathways in vitro. Upregulation of HO-1 by acteoside may involve in the neuroprotection against Aβ-induced neurotoxicity.

Topics: Amyloid beta-Peptides; Animals; Cell Death; Drug Interactions; Enzyme Activation; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Glucosides; Heme Oxygenase-1; Nerve Degeneration; Neuroprotective Agents; NF-E2-Related Factor 2; PC12 Cells; Phenols; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction; Up-Regulation

Amyloid beta-peptide (Abeta) has been implicated in the pathogenesis of AD. It can cause cell death in AD by evoking a cascade of oxidative damage to neurons. So antioxidant compounds may throw a light on the treatment of AD. In the present study, we investigated the protective effect of acteoside (AS), an antioxidative phenylethanoid glycoside, on Abeta(25-35)-induced SH-SY5Y cell injury. Exposure of cells to 25 muM Abeta(25-35) for 24 h caused viability loss, apoptotic increase and reactive oxygen species (ROS) increase, pre-treatment with acteoside for 1.5 h significantly reduced the viability loss, apoptotic rate and attenuated Abeta-mediated ROS production. In addition, AS strikingly inhibited Abeta(25-35)-induced mitochondrial dysfunctions, including lowered membrane potential, increased Bax/Bcl-2 ratio, cytochrome c release and the cleavage of caspase-3. Taken together, these results indicated that acteoside could protect SH-SY5Y cells against beta-amyloid-induced cell injury by the attenuating ROS production and the modulating apoptotic signal pathway through Bcl-2 family, cytochrome c, and caspase-3.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Caspase 3; Cell Line, Tumor; Cell Survival; Cytochromes c; Glucosides; Humans; Membrane Potential, Mitochondrial; Nerve Degeneration; Neurons; Neuroprotective Agents; Oxidative Stress; Peptide Fragments; Phenols; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species