title: Cudarflavone B provides neuroprotection against glutamate-induced mouse hippocampal HT22 cell damage through the Nrf2 and PI3K/Akt signaling pathways.
abstract: 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.
authors: Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon 400-712, Korea. dongsunglee@inha.ac.kr.
authors: Dong-Sung
authors: DS
authors: Lee
authors: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. rabis@wku.ac.kr.
authors: Wonmin
authors: W
authors: Ko
authors: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. kimman07@hanmail.net.
authors: Dong-Cheol
authors: DC
authors: Kim
authors: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. yckim@wku.ac.kr.
authors: Youn-Chul
authors: YC
authors: Kim
authors: College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 704-701, Korea. gsjeong@kmu.ac.kr.
authors: Gil-Saeng
authors: GS
authors: Jeong
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C542041:cudraflavone B; D018698:Glutamic Acid; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt