title: Nrf2-mediated HO-1 induction contributes to antioxidant capacity of a Schisandrae Fructus ethanol extract in C2C12 myoblasts.
abstract: This study was designed to confirm the protective effect of Schisandrae Fructus, which are the dried fruits of Schisandra chinensis (Turcz.) Baill, against oxidative stress-induced cellular damage and to elucidate the underlying mechanisms in C2C12 myoblasts. Preincubating C2C12 cells with a Schisandrae Fructus ethanol extract (SFEE) significantly attenuated hydrogen peroxide (H2O2)-induced inhibition of growth and induced scavenging activity against intracellular reactive oxygen species (ROS) induced by H2O2. SFEE also inhibited comet tail formation and phospho-histone γH2A.X expression, suggesting that it prevents H2O2-induced cellular DNA damage. Furthermore, treating C2C12 cells with SFEE significantly induced heme oxygenase-1 (HO-1) and phosphorylation of nuclear factor-erythroid 2 related factor 2 (Nrf2). However, zinc protoporphyrin IX, a potent inhibitor of HO-1 activity, significantly reversed the protective effects of SFEE against H2O2-induced growth inhibition and ROS generation in C2C12 cells. Additional experiments revealed that the potential of the SFEE to induce HO-1 expression and protect against H2O2-mediated cellular damage was abrogated by transient transfection with Nrf2-specific small interfering RNA, suggesting that the SFEE protected C2C12 cells against oxidative stress-induced injury through the Nrf2/HO-1 pathway.
authors.affiliation: Blue-Bio Industry Regional Innovation Center and Anti-Aging Research Center, Dongeui University, Busan 614-714, Korea. 13839@deu.ac.kr
authors.forename: Ji Sook
authors.initials: JS
authors.lastname: Kang
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Kim
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Yung
authors.initials: Y
authors.lastname: Hyun
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000737:chemistry*; D005638:Fruit; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006861:Hydrogen Peroxide / Q000633:toxicity; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D032446:Myoblasts / Q000187:drug effects* / Q000201:enzymology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D032141:Schisandra / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents / Q000737:chemistry*; D014162:Transfection
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012997:Solvents; D000431:Ethanol; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse