title: Lico A Enhances Nrf2-Mediated Defense Mechanisms against t-BHP-Induced Oxidative Stress and Cell Death via Akt and ERK Activation in RAW 264.7 Cells.
abstract: Licochalcone A (Lico A) exhibits various biological properties, including anti-inflammatory and antioxidant activities. In this study, we investigated the antioxidative potential and mechanisms of Lico A against tert-butyl hydroperoxide- (t-BHP-) induced oxidative damage in RAW 264.7 cells. Our results indicated that Lico A significantly inhibited t-BHP-induced cytotoxicity, apoptosis, and reactive oxygen species (ROS) generation and reduced glutathione (GSH) depletion but increased the glutamate-cysteine ligase modifier (GCLM) subunit and the glutamate-cysteine ligase catalytic (GCLC) subunit genes expression. Additionally, Lico A dramatically upregulated the antioxidant enzyme heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), which were associated with inducing Nrf2 nuclear translocation, decreasing Keap1 protein expression and increasing antioxidant response element (ARE) promoter activity. Lico A also obviously induced the activation of serine/threonine kinase (Akt) and extracellular signal-regulated kinase (ERK), but PI3K/Akt and ERK inhibitors treatment displayed clearly decreased levels of LicoA-induced Nrf2 nuclear translocation and HO-1 expression, respectively. Furthermore, Lico A treatment markedly attenuated t-BHP-induced oxidative damage, which was reduced by treatment with PI3K/Akt, ERK, and HO-1 inhibitors. Therefore, Lico A might have a protective role against t-BHP-induced cytotoxicity by modulating HO-1 and by scavenging ROS via the activation of the PI3K/Akt and ERK/Nrf2 signaling pathways.
authors.affiliation: Institute of Translational Medicine, Department of Ophthalmology, The First Hospital, Jilin University, Changchun 130001, China ; Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Science and Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Lv
authors.affiliation: Institute of Translational Medicine, Department of Ophthalmology, The First Hospital, Jilin University, Changchun 130001, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Ren
authors.affiliation: Institute of Translational Medicine, Department of Ophthalmology, The First Hospital, Jilin University, Changchun 130001, China.
authors.forename: Lidong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Science and Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun 130062, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Translational Medicine, Department of Ophthalmology, The First Hospital, Jilin University, Changchun 130001, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ci
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D000067996:RAW 264.7 Cells; D034622:RNA Interference; 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: D047188:Chalcones; D048049:Extracellular Signal-Regulated MAP Kinases; D005721:Glutamate-Cysteine Ligase; D051547:Heme Oxygenase-1; D051267:NF-E2-Related Factor 2; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; C560749:GCLM protein, mouse; C070840:licochalcone A