title: Icariside II enhances Nrf2 nuclear translocation to upregulate phase II detoxifying enzyme expression coupled with the ERK, Akt and JNK signaling pathways.
abstract: In the present study, the potent inducers of phase II detoxifying and antioxidant stress responsive to icariside II was investigated. First, a dose of 0-10 µM icariside II showed no significantly cytotoxicity on HepG2 cells by MTT assays and icariside II could enhance cellular GSH levels by ELISA assay. Then, the potential roles of ERK, Akt and JNK in the regulation of icariside II-induced Nrf2-dependent ARE transcriptional activity as well as ARE-mediated endogenous HO-1 and glutathione GST protein expression in HepG2 cells were estimated. Icariside II activated the nuclear translocation of Nrf2 and the up-regulated expression of Nrf2-related antioxidant protein OH-1 and GST were evaluated by Western blotting. Then the phosphorylation levels of ERK1/2, Akt and JNK1/2 were further examined by Western blotting assays. Results showed that icariside II significantly increased the phosphorylation levels of ERK1/2, Akt and JNK1/2. Furthermore, icariside II-induced ARE transcriptional activity was attenuated by the inhibition of ERK, Akt and JNK signaling using biochemical inhibitors. These results suggest that the Nrf2/ARE pathway plays an important role in the regulation of icariside-mediated antioxidant effects in HepG2 cells.
authors: Department of Anesthesiology, The Third Clinical Hospital, Harbin Medical University, Harbin 150081, China.
authors: Jing
authors: J
authors: Gu
authors: Xuechao
authors: X
authors: Sun
authors: Guonian
authors: G
authors: Wang
authors: Mingming
authors: M
authors: Li
authors: Meng
authors: M
authors: Chi
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D050217:Metabolic Detoxication, Phase II / Q000502:physiology*; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D051267:NF-E2-Related Factor 2; C060988:baohuoside I; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D005978:Glutathione