Objective: To investigate the protective effects of grape seed polyphenol extract (GSPE) against oxidative damage to human aortic endothelial cells (HAECs) induced by polycyclic aromatic hydrocarbons (PAHs), with a focus on its antioxidative mechanisms and potential regulation of Nrf2 and AhR signaling pathways.
Materials and Methods: GSPE was prepared and characterized for antioxidant activity. A cell model of benzopyrene (BaP)-induced oxidative stress in HAECs was established. Cell viability, apoptosis, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, antioxidant enzyme activity [Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GSH-Px)], mitochondrial function (membrane potential and ATP production), and Nrf2/AhR signaling pathway components were assessed using CCK-8 assay, flow cytometry, fluorescence probes, spectrophotometric analysis, and Western blotting.
Results: GSPE significantly reversed BaP-induced decreases in HAEC viability and inhibited apoptosis. It suppressed BaP-triggered ROS and MDA overproduction, restored antioxidant enzyme activity, and improved mitochondrial function (e.g. membrane potential and ATP levels). Mechanistically, GSPE modulated the Nrf2 and AhR pathways, maintaining their balanced activation to counteract oxidative stress.
Conclusion: GSPE exerts protective effects against BaP-induced oxidative damage in vascular endothelial cells by scavenging ROS and MDA, enhancing antioxidant defenses, preserving mitochondrial integrity, and regulating Nrf2/AhR signaling. These findings highlight GSPE as a potential therapeutic agent for mitigating cardiovascular risks associated with BaP exposure.