title: Hepatoprotective effect of 2'-O-galloylhyperin against oxidative stress-induced liver damage through induction of Nrf2/ARE-mediated antioxidant pathway.
abstract: 2'-O-galloylhyperin (2'-O-GH), an active compound isolated from Pyrola calliantha, possesses remarkable antioxidant activity. The aims of this study were to investigate the hepatoprotective effect of 2'-O-GH against oxidative stress and elucidate the underlying mechanistic signaling pathways in HepG2 cells as well as in an animal model. Results showed that 2'-O-GH significantly inhibited hydrogen peroxide (H2O2)-induced HepG2 cell death in a dose dependent manner. The mitogen-activated protein kinase activation, ROS production, mitochondrial membrane potential, intracellular calcium level and subsequent apoptotic protein activation in H2O2-stimulated HepG2 cells were remarkably inhibited by 2'-O-GH. Furthermore, 2'-O-GH stimulation resulted in a fast and dramatic activation of Akt and nuclear translocation of the NF-E2-related factor 2 (Nrf2), along with the increased expression of heme oxygenase-1 (HO-1) and levels of glutathione (GSH). Meanwhile, histopathological evaluation of the liver also revealed that 2'-O-GH effectively ameliorated CCl4-induced the hepatic damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Therefore, these results suggested the hepatoprotective effect of 2'-O-GH might be correlated with its antioxidant and free radical scavenger effect.
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Yi-Meng
authors.initials: YM
authors.lastname: Gao
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.affiliation: The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Province, PR China; Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Yao
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China. Electronic address: yujie_fu2002@yahoo.com.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Fu
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000187:drug effects; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D056945:Hep G2 Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D020011:Protective Agents; C087939:2''-galloylhyperin; D005707:Gallic Acid; D011794:Quercetin; D006861:Hydrogen Peroxide; D002251:Carbon Tetrachloride
keywords: 2′-O-galloylhyperin; Antioxidant gene; Hepatoprotective; Human hepatocarcinoma cell line; Nrf2; Oxidative stress