title: Protective effect of ganodermanondiol isolated from the Lingzhi mushroom against tert-butyl hydroperoxide-induced hepatotoxicity through Nrf2-mediated antioxidant enzymes.
abstract: Ganodermanondiol, a biologically active compound, was isolated from the Lingzhi mushroom (Ganoderma lucidum). The present study examined the protective effects of ganodermanondiol against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity. Ganodermanondiol protected human liver-derived HepG2 cells through nuclear factor-E2-related factor 2 (Nrf2) pathway-dependent heme oxygenase-1 expressions. Moreover, ganodermanondiol increased cellular glutathione levels and the expression of the glutamine-cysteine ligase gene in a dose-dependent manner. Furthermore, ganodermanondiol exposure enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its upstream kinase activators, LKB1 and Ca(2+)/calmodulin-dependent protein kinase-II (CaMKII). This study indicates that ganodermanondiol exhibits potent cytoprotective effects on t-BHP-induced hepatotoxicity in human liver-derived HepG2 cells, presumably through Nrf2-mediated antioxidant enzymes and AMPK.
authors.affiliation: Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Yue
authors.initials: Y
authors.lastname: Kang
authors.forename: Nai-Qi
authors.initials: NQ
authors.lastname: Yao
authors.forename: Ren-Bo
authors.initials: RB
authors.lastname: An
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000363:Agaricales / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species; D020940:Reishi; D015398:Signal Transduction; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; C050246:ganodermadiol; D007810:Lanosterol; D020122:tert-Butylhydroperoxide; D051547:Heme Oxygenase-1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D055372:AMP-Activated Protein Kinases; D005978:Glutathione