Astaxanthin Inhibits ox-LDL-Induced Early Endothelial Progenitor Cells Oxidative Stress and Apoptosis Through Nrf2 Activation.
- 1Wuhan University of Science and Technology School of Medicine Wuhan China.
- 2Department of Cardiology Wuhan Puren Hospital Wuhan China.
- 3Department of Cardiology People's Liberation Army General Hospital of Central Theater Command Wuhan China.
Abstract
Astaxanthin exerts potent protective effects against stem cell apoptosis. This study investigated the protective efficacy of astaxanthin against oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and apoptosis in endothelial progenitor cells (EPCs). Human early EPCs cultured in vitro were challenged with ox-LDL in the presence or absence of astaxanthin. Results showed that ox-LDL exposure significantly reduced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation in EPCs, while increasing oxidative stress and apoptosis rates. Astaxanthin pretreatment attenuated ox-LDL-induced reactive oxygen species (ROS) generation and EPC apoptosis, preserved mitochondrial membrane potential (MMP), and concomitantly enhanced nuclear Nrf2 accumulation while upregulating NQO1, HO-1, and glutathione (GSH) levels. Nrf2 small interfering RNA (siRNA)-mediated knockdown completely abolished astaxanthin-induced NQO1 and HO-1 upregulation. Mechanistically, astaxanthin promoted Akt phosphorylation (activation) and inhibited glycogen synthase kinase 3β (GSK-3β) phosphorylation. Pretreatment with LY294002 (a phosphoinositide 3-kinase/PI3K inhibitor) suppressed astaxanthin-induced Nrf2 nuclear translocation, exacerbated ROS production, and reduced NQO1 and GSH levels. Additionally, astaxanthin blocked ox-LDL-induced caspase-3 upregulation and preserved EPC migration and tube formation. Nrf2 siRNA eliminated the protective effects of astaxanthin on EPC ROS production, MMP preservation, apoptosis, and migration; tube formation was not assessed. Overall, these in vitro findings using cells from healthy donors provide mechanistic support for the potential role of astaxanthin in the PI3K/Akt/GSK-3/Nrf2 pathway. However, the application of astaxanthin in the prevention and treatment of atherosclerotic disease requires further validation in disease-relevant models and clinical studies, as the present study was limited to in vitro results.
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BibTeX
@article{pan2026astaxanthin,
title = {{Astaxanthin Inhibits ox-LDL-Induced Early Endothelial Progenitor Cells Oxidative Stress and Apoptosis Through Nrf2 Activation.}},
author = {Keqing Pan and Xiao Xu and Qijun Jiang and Zhigang Gong and Zhigang Li and Shifang Ding and Meichun Zhang},
journal = {Stem cells international},
year = {2026},
month = oct,
doi = {10.1155/sci/1729848},
url = {https://europepmc.org/article/MED/42948295},
note = {CC BY},
}
RIS
TY - JOUR
TI - Astaxanthin Inhibits ox-LDL-Induced Early Endothelial Progenitor Cells Oxidative Stress and Apoptosis Through Nrf2 Activation.
AU - Keqing Pan
AU - Xiao Xu
AU - Qijun Jiang
AU - Zhigang Gong
AU - Zhigang Li
AU - Shifang Ding
AU - Meichun Zhang
PY - 2026
DA - 2026/10/26
JO - Stem cells international
DO - 10.1155/sci/1729848
UR - https://europepmc.org/article/MED/42948295
AB - Astaxanthin exerts potent protective effects against stem cell apoptosis. This study investigated the protective efficacy of astaxanthin against oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and apoptosis in endothelial progenitor cells (EPCs). Human early EPCs cultured in vitro were challenged with ox-LDL in the presence or absence of astaxanthin. Results showed that ox-LDL exposure significantly reduced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation in EPCs, while increasing oxidative stress and apoptosis rates. Astaxanthin pretreatment attenuated ox-LDL-induced reactive oxygen species (ROS) generation and EPC apoptosis, preserved mitochondrial membrane potential (MMP), and concomitantly enhanced nuclear Nrf2 accumulation while upregulating NQO1, HO-1, and glutathione (GSH) levels. Nrf2 small interfering RNA (siRNA)-mediated knockdown completely abolished astaxanthin-induced NQO1 and HO-1 upregulation. Mechanistically, astaxanthin promoted Akt phosphorylation (activation) and inhibited glycogen synthase kinase 3β (GSK-3β) phosphorylation. Pretreatment with LY294002 (a phosphoinositide 3-kinase/PI3K inhibitor) suppressed astaxanthin-induced Nrf2 nuclear translocation, exacerbated ROS production, and reduced NQO1 and GSH levels. Additionally, astaxanthin blocked ox-LDL-induced caspase-3 upregulation and preserved EPC migration and tube formation. Nrf2 siRNA eliminated the protective effects of astaxanthin on EPC ROS production, MMP preservation, apoptosis, and migration; tube formation was not assessed. Overall, these in vitro findings using cells from healthy donors provide mechanistic support for the potential role of astaxanthin in the PI3K/Akt/GSK-3/Nrf2 pathway. However, the application of astaxanthin in the prevention and treatment of atherosclerotic disease requires further validation in disease-relevant models and clinical studies, as the present study was limited to in vitro results.
SN - 1687-966X
SN - 1687-9678
ER -