Biomol Ther.  2016 Jan;24(1):33-39. 10.4062/biomolther.2015.129.

Protopanaxatriol Ginsenoside Rh1 Upregulates Phase II Antioxidant Enzyme Gene Expression in Rat Primary Astrocytes: Involvement of MAP Kinases and Nrf2/ARE Signaling

• Jung JS
• Lee SY
• Kim DH
• Kim HS

• KMID: 2170538
• DOI: http://doi.org/10.4062/biomolther.2015.129

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.

Keyword

Astrocytes; Ginsenoside Rh1; Antioxidant enzyme; MAPK-Nrf2 signaling

MeSH Terms

Animals
Antioxidant Response Elements
Astrocytes*
Catalase
Cell Death
Cell Survival
DNA
Gene Expression*
Heme Oxygenase-1
Hydrogen
Neurodegenerative Diseases
Neurons
Oxidative Stress
Phosphotransferases*
Rats*
Reactive Oxygen Species
Superoxides
Up-Regulation
Catalase
DNA
Heme Oxygenase-1
Hydrogen
Phosphotransferases
Reactive Oxygen Species
Superoxides