title: The cytoprotective effect of sulfuretin against tert-butyl hydroperoxide-induced hepatotoxicity through Nrf2/ARE and JNK/ERK MAPK-mediated heme oxygenase-1 expression.
abstract: Sulfuretin is one of the major flavonoid components in Rhus verniciflua Stokes (Anacardiaceae) isolates. In this study, we investigated the protective effects of sulfuretin against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury. The results indicated that the addition of sulfuretin before t-BHP treatment significantly inhibited cytotoxicity and reactive oxygen species (ROS) production in human liver-derived HepG2 cells. Sulfuretin up-regulated the activity of the antioxidant enzyme heme oxygenase (HO)-1 via nuclear factor E2-related factor 2 (Nrf2) translocation into the nucleus and increased the promoter activity of the antioxidant response element (ARE). Moreover, sulfuretin exposure enhanced the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2), which are members of the mitogen-activated protein kinase (MAPK) family. Furthermore, cell treatment with a JNK inhibitor (SP600125) and ERK inhibitor (PD98059) reduced sulfuretin-induced HO-1 expression and decreased its protective effects. Taken together, these results suggest that the protective effect of sulfuretin against t-BHP-induced oxidative damage in human liver-derived HepG2 cells is attributable to its ability to scavenge ROS and up-regulate the activity of HO-1 through the Nrf2/ARE and JNK/ERK signaling pathways. Therefore, sulfuretin could be advantageous as a bioactive source for the prevention of oxidative injury.
authors.affiliation: Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Korea. hsds@wku.ac.kr.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. pipo5@wku.ac.kr.
authors.forename: Kyoung-Su
authors.initials: KS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. rabis815@naver.com.
authors.forename: Wonmin
authors.initials: W
authors.lastname: Ko
authors.affiliation: Department of Pharmacy, Qingdao University of Science & Technology, Qingdao 266042, China. leebin09@naver.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: College of Pharmacy, Keimyung University, Dae-gu 704-701, Korea. gsjeong@kmu.ac.kr.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, Inha University School of Medicine, Incheon 400-712, Korea. juhjang@inha.ac.kr.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Korea. hoh@wku.ac.kr.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.affiliation: Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Korea. yckim@wku.ac.kr.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D061745:Antioxidant Response Elements / Q000187:drug effects*; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D000873:Anthracenes; D001572:Benzofurans; D005419:Flavonoids; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D017382:Reactive Oxygen Species; C432165:pyrazolanthrone; D020122:tert-Butylhydroperoxide; D051547:Heme Oxygenase-1; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C054989:sulfuretin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one