In vitro and in vivo hepatoprotective effect of ganodermanontriol against t-BHP-induced oxidative stress

TY - JOUR

T1 - In vitro and in vivo hepatoprotective effect of ganodermanontriol against t-BHP-induced oxidative stress

AU - Ha, Do Thi

AU - Oh, Joonseok

AU - Khoi, Nguyen Minh

AU - Dao, Trong Tuan

AU - Dung, Le Viet

AU - Do, Thi Nguyet Que

AU - Lee, Sang Myung

AU - Jang, Tae Su

AU - Jeong, Gil-Saeng

AU - Na, MinKyun

N1 - © 2013 Elsevier Ireland Ltd. All rights reserved.

PY - 2013/12/12

Y1 - 2013/12/12

N2 - 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.

AB - 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.

KW - Alanine Transaminase

KW - Animals

KW - Aspartate Aminotransferases

KW - Cell Line, Tumor

KW - Drug-Induced Liver Injury

KW - Fruit

KW - Ganoderma

KW - Glutathione

KW - Heme Oxygenase-1

KW - Lanosterol

KW - Male

KW - Membrane Proteins

KW - Mice

KW - Mice, Inbred ICR

KW - Mitogen-Activated Protein Kinases

KW - NF-E2-Related Factor 2

KW - Oxidative Stress

KW - Phosphatidylinositol 3-Kinases

KW - Plant Extracts

KW - Protective Agents

KW - Proto-Oncogene Proteins c-akt

KW - tert-Butylhydroperoxide

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jep.2013.09.039

DO - 10.1016/j.jep.2013.09.039

M3 - Journal article

C2 - 24140584

SN - 0378-8741

VL - 150

SP - 875

EP - 885

JO - Journal of Ethnopharmacology

JF - Journal of Ethnopharmacology

IS - 3

ER -