title: 3',4',7-Trihydroxyflavone prevents apoptotic cell death in neuronal cells from hydrogen peroxide-induced oxidative stress.
abstract: In this study, we investigated the mechanisms of 3',4',7-trihydroxyflavone (THF) protection of neuronal cells from neuronal cell death induced by the oxidative stress-related neurotoxin hydrogen peroxide (H2O2). Pretreatment with THF significantly elevated cell viability, reduced H2O2-induced lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production, glutathione (GSH) content, superoxide dismutase (SOD) activity, catalase (CAT) activity, and mitochondria membrane potential (MMP) loss. Western blot data demonstrated that THF inhibited the H2O2-induced up- or down-regulation of cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), Bax, Bcl-2, and Bcl-xL, and attenuated the H2O2-induced release of cytochrome c from the mitochondria to the cytosol. In addition, pretreatment with THF attenuated H2O2-induced rapid and significant phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinases (PI3K)/Akt. THF also inhibited nuclear factor-κB (NF-κB) translocation to the nucleus induced by H2O2, down-stream of H2O2-induced phosphorylation of MAPKs and PI3K/Akt. These data provide the first evidence that THF protects neuronal cells against H2O2-induced oxidative stress, possibly through ROS reduction, mitochondria protection, and NF-κB modulation via MAPKs and PI3K/Akt pathways. The neuroprotective effects of THF make it a promising candidate as a therapeutic agent for neurodegenerative diseases.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, South Korea; Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
authors.forename: Sa-Ik
authors.initials: SI
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
authors.forename: Shi-Xun
authors.initials: SX
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea. Electronic address: jang@skku.edu.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species
chemical_list: C587591:3',4',7-trihydroxyflavone; D005419:Flavonoids; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide
keywords: 3′,4′,7-Trihydroxyflavone; Apoptotic cell death; Hydrogen peroxide; Neuronal cells; Oxidative stress