Study on the role of naringin in attenuating Trimethylamine-N-Oxide-Induced human umbilical vein endothelial cell inflammation, oxidative stress, and endothelial dysfunction.

Abstract

Trimethylamine-N-oxide (TMAO), a phospholipid metabolite, can modulate cholesterol synthesis and promote vascular inflammation and endothelial dysfunction, thereby increasing the risk of atherosclerosis (AS). Previously, it was found that naringin reduced damage to human umbilical vein endothelial cells (HUVECs) triggered by oxidized low-density lipoprotein. This article continues to explore the role and mechanism of naringin in protecting HUVECs from TMAO-induced damage. After the construction of TMAO-induced AS model in HUVECs, inflammation, oxidative stress, and endothelial function were examined by real-time quantitative polymerase chain reaction, Western blotting, nitric oxide (NO), reactive oxygen species (ROS), superoxide dismutase, and malondialdehyde (MDA) kits. Results showed that naringin pretreatment inhibited endothelial inflammation and oxidative stress, promoted NO release, and inhibited the degradation of Zona occludens-2, occludin, and vascular endothelial-cadherin, thereby restoring the functional and structural integrity of the endothelium. Furthermore, the addition of mitogen-activated protein kinase (MAPK) agonist demonstrated that the therapeutic effect of naringin was achieved through inactivating TMAO-stimulated MAPK signaling in HUVECs.