Protopanaxatriol Ginsenoside Rh1 Upregulates Phase II Antioxidant Enzyme Gene Expression in Rat Primary Astrocytes: Involvement of MAP Kinases and Nrf2/ARE Signaling.
10.4062/biomolther.2015.129
- Author:
Ji Sun JUNG
1
;
Sang Yoon LEE
;
Dong Hyun KIM
;
Hee Sun KIM
Author Information
1. Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School, Seoul 07985, Republic of Korea. hskimp@ewha.ac.kr
- Publication Type:Original Article
- Keywords:
Astrocytes;
Ginsenoside Rh1;
Antioxidant enzyme;
MAPK-Nrf2 signaling
- MeSH:
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
- From:Biomolecules & Therapeutics
2016;24(1):33-39
- CountryRepublic of Korea
- Language:English
-
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.
