Ginsenoside Rb1 Blocks Ritonavir-Induced Oxidative Stress and eNOS Downregulation through Activation of Estrogen Receptor-Beta and Upregulation of SOD in Human Endothelial Cells.
Int J Mol Sci
; 20(2)2019 Jan 12.
Article
em En
| MEDLINE
| ID: mdl-30642080
ABSTRACT
We have previously shown that ritonavir (RTV), a highly active anti-retroviral therapy (HAART) drug, can cause endothelial dysfunction through oxidative stress. Several antioxidants including ginsenoside Rb1, a compound with antioxidant effect, can effectively block this side effect of RTV in endothelial cells. In the current study, we explored a mechanism by which ginsenoside Rb1 could protect these cells via binding of estrogen receptors (ERs). We found that several human endothelial cell lines differentially expressed ER-ß and had very low levels of ER-α. RTV treatment significantly increased the production of reactive oxygen species (ROS) and decreased the expression of endothelial nitric oxidase synthase (eNOS) and superoxide dismutase (SOD) in HUVECs, while Rb1 effectively blocked these effects of RTV. These effects of Rb1 were effectively inhibited by silencing ER-ß, indicating that ginsenoside Rb1 requires ER-ß for its antioxidant activity in inhibiting the deleterious effect of RTV in human endothelial cells. Furthermore, Rb1 specifically activated ER-ß transactivation activity by ER-ß luciferase reporter assay. Rb1 competitively bound to ER-ß, which was determined by the high sensitive fluorescent polarization assay.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Superóxido Dismutase
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Ritonavir
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Ginsenosídeos
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Células Endoteliais
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Receptor beta de Estrogênio
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Óxido Nítrico Sintase Tipo III
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article