کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2582927 | 1130675 | 2015 | 8 صفحه PDF | دانلود رایگان |

• α-Iso-cubebenol showed protective effects in glutamate-induced HT22 cell death.
• Glutamate-induced accumulation of ROS and calcium was reduced by α-iso-cubebenol.
• α-Iso-cubebenol activated CREB and Nrf-2 pathways in HT22 cells.
• α-Iso-cubebenol increased the levels of enzymes HO-1 and NQO1 in HT22 cells.
• CREB and Nrf-2 participated in the neuroprotective effects of α-iso-cubebenol.
α-Iso-cubebenol is a natural compound isolated from Schisandra chinensis, and is reported to have beneficial bioactivity including anti-inflammatory and anti-tumor activities. Glutamate-induced oxidative neuronal damage has been implicated in a variety of neurodegenerative disorders. Here we investigated the mechanisms of α-iso-cubebenol protection of mouse hippocampus-derived neuronal cells (HT22 cells) from apoptotic cell death induced by the major excitatory neurotransmitter, glutamate. Pretreatment with α-iso-cubebenol markedly attenuated glutamate-induced loss of cell viability and release of lactate dehydrogenase), in a dose-dependent manner. α-Iso-cubebenol significantly reduced glutamate-induced intracellular reactive oxygen species and calcium accumulation. Strikingly, α-iso-cubebenol inhibited glutamate-induced mitochondrial depolarization, which releases apoptosis-inducing factor from mitochondria. α-Iso-cubebenol also suppressed glutamate-induced phosphorylation of extracellular-signal-regulated kinases. Furthermore, α-iso-cubebenol induced CREB phosphorylation and Nrf-2 nuclear accumulation and increased the promoter activity of ARE and CREB in HT22 cells. α-Iso-cubebenol also upregulated the expression of phase-II detoxifying/antioxidant enzymes such as HO-1 and NQO1. Subsequent studies revealed that the inhibitory effects of α-iso-cubebenol on glutamate-induced apoptosis were abolished by small interfering RNA-mediated knockdown of CREB and Nrf-2. These findings suggest that α-iso-cubebenol prevents excitotoxin-induced oxidative damage to neurons by inhibiting apoptotic cell death, and might be a potential preventive or therapeutic agent for neurodegenerative disorders.
Journal: Environmental Toxicology and Pharmacology - Volume 40, Issue 2, September 2015, Pages 549–556