title: Gastrodia elata shows neuroprotective effects via activation of PI3K signaling against oxidative glutamate toxicity in HT22 cells.
abstract: Dried roots of Gastrodia elata have traditionally been used in Korean medicine for the treatment of neurological disorders such as scotodinia, paralysis, and epilepsy. In our study, we attempted to investigate the neuroprotective effects of methanol extract from G. elata (MEGE) against glutamate-mediated oxidative stress and to explore underlying neuroprotective mechanisms. Analyses for cell viability, lactate dehydrogenase (LDH), flow cytometry, Western blot, and reactive oxygen species (ROS) were performed in HT22 hippocampal cells. Pretreatment with MEGE resulted in a potent neuroprotective effect against oxidative glutamate toxicity and these effects were exerted mainly by the abrogation of glutamate-induced apoptotic death. Treatment with glutamate resulted in a significant expression of both phosphorylated p38 and dephosphorylated phosphatidylinositol-3-kinase (PI3K). However, pretreatment with MEGE resulted in the inhibition of these expressions. In the inhibitor studies, treatment with PI3K inhibitor LY294002 resulted in the abrogation of the neuroprotective effect of MEGE. In addition, pretreatment with MEGE also resulted in the suppression of the glutamate-induced production of ROS. Treatment with MEGE and anti-oxidant N-acetyl-L-cysteine (NAC) resulted in the enhanced phosphorylation of both PI3K and cAMP responsive element binding protein (CREB), and, in particular, treatment with MEGE resulted in significantly enhanced expression of mature brain-derived neurotrophic factor (BDNF). These results suggest that the extract from G. elata mainly exerted neuroprotective effects through the up-regulation of the PI3K signaling pathway in association with BDNF and may be a useful therapeutic agent for treatment of oxidative neuronal death.
authors.affiliation: Department of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors.forename: Ye Jin
authors.initials: YJ
authors.lastname: Han
authors.forename: Ju Hui
authors.initials: JH
authors.lastname: Je
authors.forename: So Hyoung
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Ahn
authors.forename: Ha Neui
authors.initials: HN
authors.lastname: Kim
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Choi
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D031668:Gastrodia; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D058539:Phosphatidylinositol 3-Kinase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Gastrodia elata; HT22 Cell; Oxidative Toxicity; PI3K