Neuroprotective effects of α-iso-cubebenol on glutamate-induced neurotoxicity

Environmental Toxicology and Pharmacology
Sun Young ParkYoung-Whan Choi

Abstract

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...Continue Reading

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Citations

Mar 26, 2016·Journal of Agricultural and Food Chemistry·Ji Yeon SeoJong-Sang Kim
Feb 14, 2019·Connective Tissue Research·Ra Jeong KimHyung Bin Park
Jul 20, 2019·Phytotherapy Research : PTR·Alireza TavakkoliGholamreza Karimi
Jul 3, 2018·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Byeong Hyeok YeChi Dae Kim
Dec 6, 2016·Frontiers in Microbiology·Rahul MittalXue Z Liu

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