title: Antioxidant activity of 7,8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity.
abstract: Glutamate, an excitatory neurotransmitter in the central nervous system, plays an important role in neurological disorders. Previous studies have shown that excess glutamate can cause oxidative stress in a hippocampal HT-22 cell line. 7,8-Dihydroxyflavone (7,8-DHF), a member of the flavonoid family, is a selective tyrosine kinase receptor B (TrkB) agonist that has neurotrophic effects in various neurological diseases such as stroke and Parkinson's disease. In this study, we found that there is no TrkB receptor in HT-22 cells. Despite this, our data demonstrate that 7,8-DHF still protects against glutamate-induced toxicity in HT-22 cells in a concentration-dependent manner, indicating that 7,8-DHF prevents cell death through other mechanisms rather than TrkB receptors in this cell model. We further show that 7,8-DHF increases cellular glutathione levels and reduces reactive oxygen species (ROS) production caused by glutamate in HT-22 cells. Finally, our data demonstrate that 7,8-DHF protects against hydrogen peroxide and menadione-induced cell death, suggesting that 7,8-DHF has an antioxidant effect. In summary, although 7,8-DHF is considered as a selective TrkB agonist, our results demonstrate that 7,8-DHF can still confer neuroprotection against glutamate-induced toxicity in HT-22 cells via its antioxidant activity.
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou City, Jiangsu Province 215004, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Kao-Wei
authors.initials: KW
authors.lastname: Chua
authors.forename: Chu C
authors.initials: CC
authors.lastname: Chua
authors.forename: Hailong
authors.initials: H
authors.lastname: Yu
authors.forename: Aijie
authors.initials: A
authors.lastname: Pei
authors.forename: Balvin H L
authors.initials: BH
authors.lastname: Chua
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Hamdy
authors.forename: Xingshun
authors.initials: X
authors.lastname: Xu
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D024483:Vitamin K 3 / Q000037:antagonists & inhibitors / Q000633:toxicity
chemical_list: C485383:6,7-dihydroxyflavone; D000975:Antioxidants; D047309:Flavones; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D024483:Vitamin K 3; D006861:Hydrogen Peroxide; D005978:Glutathione