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J Ethnopharmacol ; 150(3): 875-85, 2013 Dec 12.
Article in English | MEDLINE | ID: mdl-24140584

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Fr.) Karst. (Ganodermataceae) is a mushroom which is used as a traditional remedy in the treatment of human diseases such as hepatitis, liver disorders, hypercholesterolemia, arthritis, bronchitis and tumorigenic diseases. This study targets the evaluation of hepatoprotective activity of ganodermanontriol, a sterol isolated from Ganoderma lucidum, and the investigation of its mechanism of action in Hepa1c1c7 and murine liver cells upon tert-butyl hydroperoxide (t-BHP)-induced inflammation. t-BHP was utilized to stimulate an anti-inflammatory reaction in the hepatic cell lines and murine hepatic tissue examined. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-PCR) were used to estimate the expression of ganodermanontriol (GDT)-induced proteins, including heme oxidase-1 (HO-1) and mitogen-activated protein kinases (MAPKs) as well as the corresponding mRNA. Luciferase assays were conducted to evaluate the interaction between NF-E2-related factor-2 (Nrf-2), the antioxidant response element (ARE), and the promoter region of the HO-1 gene and subsequent gene expression. Biochemical markers for hepatotoxicity were monitored to assess whether GDT protected the cells from the t-BHP-mediated oxidative stimuli. RESULTS: GDT induced HO-1 expression via the activation of Nrf-2 nuclear translocation and the subsequent transcription of the HO-1 gene in vitro and in vivo, which seemed to be regulated by phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and p38 signaling pathways. GDT exhibited in vitro and in vivo hepatoprotective activity as determined by the lowered levels of hepatic enzymes and malondialdehydes and the elevated glutathione levels. CONCLUSIONS: This study validates the ethnopharmacological application of Ganoderma lucidum as a treatment for hepatic disorders. GDT induced in vitro and in vivo anti-inflammatory activity in t-BHP-damaged hepatic cells through the expression of HO-1, and in which PI3K/Akt and p38 kinases are involved. Our study motivates further research in the exploration of potent hepatoprotective agents from Ganoderma lucidum.


Subject(s)
Lanosterol/analogs & derivatives , Oxidative Stress/drug effects , Protective Agents/pharmacology , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Cell Line, Tumor , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Fruit , Ganoderma , Glutathione/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Lanosterol/pharmacology , Lanosterol/therapeutic use , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Inbred ICR , Mitogen-Activated Protein Kinases/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Plant Extracts , Protective Agents/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , tert-Butylhydroperoxide
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