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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / genetics
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AMP-Activated Protein Kinases / metabolism
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Agaricales / chemistry
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Antioxidants / pharmacology*
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
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Cytoprotection / drug effects
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Drugs, Chinese Herbal / chemistry*
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Glutathione / metabolism
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Heme Oxygenase-1 / genetics
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Heme Oxygenase-1 / metabolism
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Hep G2 Cells
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Humans
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Lanosterol / analogs & derivatives*
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Lanosterol / pharmacology
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Liver / drug effects*
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Liver / enzymology
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Liver / pathology
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NF-E2-Related Factor 2 / genetics*
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NF-E2-Related Factor 2 / metabolism
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Phosphorylation
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Reactive Oxygen Species
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Reishi
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Signal Transduction
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tert-Butylhydroperoxide / toxicity*
Substances
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Antioxidants
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Drugs, Chinese Herbal
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NF-E2-Related Factor 2
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NFE2L2 protein, human
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Reactive Oxygen Species
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ganodermadiol
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Lanosterol
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tert-Butylhydroperoxide
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Heme Oxygenase-1
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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AMP-Activated Protein Kinases
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Glutathione