title: Isoliquiritigenin in licorice functions as a hepatic protectant by induction of antioxidant genes through extracellular signal-regulated kinase-mediated NF-E2-related factor-2 signaling pathway.
abstract: OBJECTIVE
  Liver is the major site of biotransformation for exogenous toxins, in having a defense system against oxidative stress as well as cytochrome P450 system. Isoliquiritigenin (isoLQ) is an active component present in Glycyrrhizae radix and has been shown to have various biological activities. This study investigated the effect of isoLQ as a liver protectant against oxidative stress, both in vivo and in vitro, and also its molecular mechanisms.
  
  
  METHODS
  We used tert-butylhydroperoxide-induced hepatocyte damage model and cadmium (Cd)-stimulated liver toxicity animal model, which are assessed by immunoblot and flow cytometry as well as plasma and histopathological parameters.
  
  
  RESULTS
  In HepG2 cells, pretreatment of 10 and 30 µM isoLQ significantly inhibited the induction of apoptosis and mitochondrial damage, and production of reactive oxygen species. Moreover, isoLQ induced the activation of nuclear factor erythroid 2-related factor-2 (Nrf2), as indicated by an increase in its nuclear translocation and antioxidant response element-luciferase activity. IsoLQ also induced the expression of Nrf2 target phase II enzymes, such as heme oxygenase-1, glutamate-cysteine ligase catalytic subunit and NAD(P)H:quinone oxidoreductase 1. IsoLQ also induced phosphorylation of extracellular stimuli-regulated kinase (ERK), and its activation of Nrf2 was mediated with ERK-dependent phosphorylation of Nrf2, as determined by its chemical inhibitor. In rats, oral treatment of 5 and 20 mg/kg isoLQ prevented Cd-induced acute hepatic damage, as assessed by plasma parameters and semiquantative histology, such as the modified HAI grading scores and the degenerative regions in hepatic parenchyma.
  
  
  CONCLUSIONS
  These findings are considered as scientific evidence that isoLQ in licorice has the function of being a hepatic protectant against oxidative damages through ERK-mediated Nrf2 activation.
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea.
authors.forename: Sang Mi
authors.initials: SM
authors.lastname: Park
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea.
authors.forename: Jong Rok
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea.
authors.forename: Sae Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea.
authors.forename: Il Je
authors.initials: IJ
authors.lastname: Cho
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea.
authors.forename: Sung Hui
authors.initials: SH
authors.lastname: Byun
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea.
authors.forename: Sang Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea. haany@dhu.ac.kr.
authors.forename: Sook Jahr
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbuk-do, 712-715, South Korea. ywkim@dhu.ac.kr.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002104:Cadmium / Q000633:toxicity; D047188:Chalcones / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D006035:Glycyrrhiza / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D015415:Biomarkers; D047188:Chalcones; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D020011:Protective Agents; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D002104:Cadmium; C040920:isoliquiritigenin; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase
keywords: ERK; Isoliquiritigenin; Liver protectant; Nrf2; Oxidative stress