Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/ijms20020294
Keywords
ginsenoside Rb1; ritonavir; oxidative stress; endothelial nitric oxidase synthase; estrogen receptor; superoxide dismutase; endothelial dysfunction
Funding
- National Institutes of Health [R01 HL083471]
- NIH [T32HL083774]
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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-beta and had very low levels of ER-alpha. 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-beta, indicating that ginsenoside Rb1 requires ER-beta for its antioxidant activity in inhibiting the deleterious effect of RTV in human endothelial cells. Furthermore, Rb1 specifically activated ER-beta transactivation activity by ER-beta luciferase reporter assay. Rb1 competitively bound to ER-beta, which was determined by the high sensitive fluorescent polarization assay.
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