title: Mitochondria protection of baicalein against oxidative damage via induction of manganese superoxide dismutase.
abstract: This study investigated the cytoprotective effect of baicalein (5,6,7-trihydroxyflavone) against oxidative stress-induced mitochondrial dysfunction. Electron spin resonance (ESR) spectrometry revealed that baicalein showed significant scavenging effects on superoxide radicals and hydroxyl radicals. When H(2)O(2) treatment induces an increase in mitochondrial reactive oxygen species (ROS), baicalein treatment decreased high level of ROS. Baicalein significantly reduced alteration of Bcl-2 family proteins, the release of cytochrome c from mitochondria into the cytosol via inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1) and c-Jun NH(2)-terminal kinase (JNK) cascades induced by H(2)O(2) treatment. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme in mitochondria against oxidative stress. Baicalein restored both MnSOD protein expression and activity, which were abolished by H(2)O(2) treatment. The transcription factor NF-E2-related factor 2 (Nrf2) is a critical regulator of MnSOD, achieved by binding to the antioxidant response element (ARE). Baicalein restored nuclear Nrf2 protein expression and its ARE binding activity, which were abolished by H(2)O(2) treatment. These studies demonstrate that baicalein attenuates mitochondrial oxidative stress by activating Nrf2-mediated MnSOD induction.
authors.affiliation: Department of Microbiology and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: In Kyung
authors.initials: IK
authors.lastname: Lee
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Bum Joon
authors.initials: BJ
authors.lastname: Kim
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002458:Cell Fractionation; D002470:Cell Survival; D002474:Cell-Free System; D004396:Coloring Agents; D006224:Cricetinae; D053938:DNA Fragmentation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D044950:Flavanones / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D007202:Indicators and Reagents; D008928:Mitochondria / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D013481:Superoxides / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000975:Antioxidants; D004396:Coloring Agents; D044950:Flavanones; D007202:Indicators and Reagents; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D013481:Superoxides; D017665:Hydroxyl Radical; C006680:baicalein; D013482:Superoxide Dismutase; C022616:thiazolyl blue