Icariside II Enhances Nrf2 Nuclear Translocation to Upregulate Phase II Detoxifying Enzyme Expression Coupled with the ERK, Akt and JNK Signaling Pathways
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 as...
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MDPI AG
2011-11-01
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Series: | Molecules |
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Online Access: | http://www.mdpi.com/1420-3049/16/11/9234/ |
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author | Meng Chi Guonian Wang Mingming Li Xuechao Sun Jing Gu |
author_facet | Meng Chi Guonian Wang Mingming Li Xuechao Sun Jing Gu |
author_sort | Meng Chi |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-35c8609abf3e4f169bec2abc7f378bec2022-12-22T03:45:10ZengMDPI AGMolecules1420-30492011-11-0116119234924410.3390/molecules16119234Icariside II Enhances Nrf2 Nuclear Translocation to Upregulate Phase II Detoxifying Enzyme Expression Coupled with the ERK, Akt and JNK Signaling PathwaysMeng ChiGuonian WangMingming LiXuechao SunJing GuIn 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.http://www.mdpi.com/1420-3049/16/11/9234/icariside IINrf2ERKAktJNKHepG2 cells |
spellingShingle | Meng Chi Guonian Wang Mingming Li Xuechao Sun Jing Gu Icariside II Enhances Nrf2 Nuclear Translocation to Upregulate Phase II Detoxifying Enzyme Expression Coupled with the ERK, Akt and JNK Signaling Pathways Molecules icariside II Nrf2 ERK Akt JNK HepG2 cells |
title | Icariside II Enhances Nrf2 Nuclear Translocation to Upregulate Phase II Detoxifying Enzyme Expression Coupled with the ERK, Akt and JNK Signaling Pathways |
title_full | Icariside II Enhances Nrf2 Nuclear Translocation to Upregulate Phase II Detoxifying Enzyme Expression Coupled with the ERK, Akt and JNK Signaling Pathways |
title_fullStr | Icariside II Enhances Nrf2 Nuclear Translocation to Upregulate Phase II Detoxifying Enzyme Expression Coupled with the ERK, Akt and JNK Signaling Pathways |
title_full_unstemmed | Icariside II Enhances Nrf2 Nuclear Translocation to Upregulate Phase II Detoxifying Enzyme Expression Coupled with the ERK, Akt and JNK Signaling Pathways |
title_short | Icariside II Enhances Nrf2 Nuclear Translocation to Upregulate Phase II Detoxifying Enzyme Expression Coupled with the ERK, Akt and JNK Signaling Pathways |
title_sort | icariside ii enhances nrf2 nuclear translocation to upregulate phase ii detoxifying enzyme expression coupled with the erk akt and jnk signaling pathways |
topic | icariside II Nrf2 ERK Akt JNK HepG2 cells |
url | http://www.mdpi.com/1420-3049/16/11/9234/ |
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