Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Protopanaxatriol Ginsenoside Rh1 Upregulates Phase II Antioxidant Enzyme Gene Expression in Rat Primary Astrocytes: Involvement of MAP Kinases and Nrf2/ARE Signaling

  • Jung, Ji-Sun (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School) ;
  • Lee, Sang-Yoon (Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Kim, Dong-Hyun (Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Kim, Hee-Sun (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School)
  • Received : 2015.08.17
  • Accepted : 2015.09.04
  • Published : 2016.01.01
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Abstract

Oxidative stress activates several intracellular signaling cascades that may have deleterious effects on neuronal cell survival. Thus, controlling oxidative stress has been suggested as an important strategy for prevention and/or treatment of neurodegenerative diseases. In this study, we found that ginsenoside Rh1 inhibited hydrogen peroxide-induced reactive oxygen species generation and subsequent cell death in rat primary astrocytes. Rh1 increased the expression of phase II antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1, superoxide dismutase-2, and catalase, that are under the control of Nrf2/ARE signaling pathways. Further mechanistic studies showed that Rh1 increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to the antioxidant response element (ARE), and increased the ARE-mediated transcription activities in rat primary astrocytes. Analysis of signaling pathways revealed that MAP kinases are important in HO-1 expression, and act by modulating ARE-mediated transcriptional activity. Therefore, the upregulation of antioxidant enzymes by Rh1 may provide preventive therapeutic potential for various neurodegenerative diseases that are associated with oxidative stress.

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References

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