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Journal of Integrative Medicine: 2019   Online First

DOI: 10.1016/j.joim.2019.01.011
Research Article
Icariin protects vascular endothelial cells from oxidative stress through inhibiting endoplasmic reticulum stress
1. Fang-yuan Wang (Department of Traditional Chinese Medicine, Army Medical Center in Traditional Chinese Medicine, Xijing Hospital, Forth Military Medical University, Xi’an 710032, Shaanxi Province, China )
2. Jian Jia (Department of Traditional Chinese Medicine, Army Medical Center in Traditional Chinese Medicine, Xijing Hospital, Forth Military Medical University, Xi’an 710032, Shaanxi Province, China )
3. Huan-huan Song (Department of Traditional Chinese Medicine, Army Medical Center in Traditional Chinese Medicine, Xijing Hospital, Forth Military Medical University, Xi’an 710032, Shaanxi Province, China )
4. Cheng-ming Jia (Department of Traditional Chinese Medicine, Army Medical Center in Traditional Chinese Medicine, Xijing Hospital, Forth Military Medical University, Xi’an 710032, Shaanxi Province, China )
5. Chang-bo Chen (Department of Traditional Chinese Medicine, Army Medical Center in Traditional Chinese Medicine, Xijing Hospital, Forth Military Medical University, Xi’an 710032, Shaanxi Province, China )
6. Jing Ma (Department of Traditional Chinese Medicine, Army Medical Center in Traditional Chinese Medicine, Xijing Hospital, Forth Military Medical University, Xi’an 710032, Shaanxi Province, China )

 Abstract
Objective

To investigate the protective effect and underlying mechanism(s) of icariin (ICA) in preventing hydrogen peroxide (H2O2)-induced vascular endothelial cell injury via endoplasmic reticulum stress (ERS).
Methods
To study the effects of ICA on H2O2-induced damage, we used the cell counting kit-8 assay to detect cell viability and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay to determine cell adhesion and apoptosis, respectively. Spectrophotometry and enzyme-linked immunosorbent assay were used to measure the expression levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Subsequently, glucose-regulated protein 78 (GRP78), activating transcription factor-4 (ATF4) and eukaryotic initiation factor-2α (eIF2α) were detected using Western blotting.
Results
In human umbilical vein endothelial cells, different concentrations of ICA exhibited multiple effects, including reduced H2O2 damage, improved cell viability and adhesion, reduced cell apoptosis and increased SOD and GSH-Px activity. Among the ICA concentrations used, only the H2O2 + 100 μmol/L ICA group had significant differences compared to the H2O2 group. ERS activators H2O2 and DL-dithiothreitol (DTT) significantly increased GRP78, ATF4 and eIF2α expressions, decreased cell activity and reduced SOD and GSH-Px activity. In contrast, the H2O2 + 100 μmol/L ICA and H2O2 + 100 μmol/L ICA + DTT groups had significant inhibitory effects on the expressions of GRP78, ATF4 and eIF2α proteins, showed enhanced cell viability and SOD and GSH-Px activity.
Conclusion
The results showed the dose-dependent effects of ICA against H2O2-induced injury in vascular endothelial cells. The inhibition of GRP78, ATF4 and eIF2α protein expressions in the ERS, and the subsequent alleviation of oxidative stress damage, might be the molecular mechanism.

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Please cite this article as:
Wang FY, Jia J, Song HH, Jia CM, Chen CB, Ma J. Icariin protects vascular endothelial cells from oxidative stress through inhibiting endoplasmic reticulum stress. J Integr Med. 2019; Epub ahead of print.
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