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In vitro and in vivo hepatoprotective effect of ganodermanontriol against t-BHP-induced oxidative stress
- Ha, Do Thi, Oh, Joonseok, Minh Khoi, Nguyen, Dao, Trong Tuan, Dung, Le Viet, Do, Thi Nguyet Que, Lee, Sang Myung, Jang, Tae Su, Jeong, Gil-Saeng, Na, MinKyun
- Journal of ethnopharmacology 2013 v.150 no.3 pp. 875-885
- anti-inflammatory activity, hepatitis, luciferase, arthritis, Western blotting, genes, hypercholesterolemia, promoter regions, mitogen-activated protein kinase, oxidative stress, mechanism of action, biomarkers, gene expression, mushrooms, hepatoprotective effect, bronchitis, human diseases, messenger RNA, polymerase chain reaction, hepatocytes, phosphatidylinositol 3-kinase, liver, Ganoderma lucidum, inflammation, karsts, hepatotoxicity
- 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.