Antioxidant Activity of 7,8-Dihydroxyflavone Provides Neuroprotection Against Glutamate-Induced Toxicity
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.
Chen, Jing; Chua, Kao Wei; Chua, Chu C.; Yu, Hailong; Pei, Aijie; Chua, Balvin H.L.; Hamdy, Ronald C.; Xu, Xingshun; and Liu, Chun Feng. 2011. Antioxidant Activity of 7,8-Dihydroxyflavone Provides Neuroprotection Against Glutamate-Induced Toxicity. Neuroscience Letters. Vol.499(3). 181-185. https://doi.org/10.1016/j.neulet.2011.05.054 PMID: 21651962 ISSN: 0304-3940