Cudarflavone B Provides Neuroprotection against Glutamate-Induced Mouse Hippocampal HT22 Cell Damage through the Nrf2 and PI3K/Akt Signaling Pathways

Molecules

Dong-Sung Lee¹  Wonmin Ko²  Dong-Cheol Kim²  Youn-Chul Kim² 

[1] Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon 400-712, Korea; E-Mail:;College of Pharmacy, Wonkwang University, Iksan 570-749, Korea; E-Mails:

关键词: cudraflavone B;    glutamate;    oxidative stress;    neuroprotection;    mouse hippocampalHT22;    nuclear factor-E2-related factor 2;    heme oxygenase-1;   

DOI  :  10.3390/molecules190810818

来源: mdpi

【 摘 要 】

Oxidative cell damage contributes to neuronal degeneration in many central nervous system (CNS) diseases such as Alzheimer’s disease, Parkinson’s disease, and ischemia. Nrf2 signaling-mediated heme oxygenase (HO)-1 expression acts against oxidants that are thought to play a key role in the pathogenesis of neuronal diseases. Cudraflavone B is a prenylated flavone isolated from C. tricuspidata which has shown anti-proliferative activity, mouse brain monoamine oxidase (MAO) inhibitory effects, apoptotic actions in human gastric carcinoma cells and mouse melanoma cells, and hepatoprotective activity. In this study, cudraflavone B showed neuroprotective effects and reactive oxygen species (ROS) inhibition against glutamate-induced neurotoxicity by inducing the expression of HO-1 in mouse hippocampal HT22 cells. Furthermore, cudraflavone B caused the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (ARE) in mouse hippocampal HT22 cells. In addition, we found that the Nrf2-midiated HO-1 expression by cudraflavone B is involved in the cell protective response and ROS reductions, and cudraflavone B-induced expression of HO-1 was mediated through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in HT22 cells. Our results demonstrated the potential application of naturally occurring cudraflavone B as a therapeutic agent from neurodegenerative disease.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.