Myricetin Inhibits Mitochondrial Dysfunction and Oxidative Stress in Trimethylamine N-Oxide-Induced Human Umbilical Vein Endothelial Cells
TL;DR
These findings demonstrate that MYR protects against mitochondrial dysfunction and oxidative stress in HUVECs, likely through associated antioxidant properties and activation of the NRF2 signaling pathway.
Abstract
Background:Myricetin (MYR) has attracted significant attention for its broad range of biological activities, including anti-inflammatory, anti-cancer, and anti-obesity effects. MYR also exerts notable protective effects against cardiovascular diseases and osteoporosis. Thus, this study aimed to investigate the therapeutic potential and underlying mechanisms of MYR in alleviating trimethylamine N-oxide (TMAO)-induced mitochondrial dysfunction and oxidative stress in human umbilical vein endothelial cells (HUVECs), thereby providing insights into potential strategies for treating atherosclerosis.Methods:Mitochondrial dysfunction and oxidative stress in vitro were modeled by treating HUVECs with TMAO. The protective effects of MYR were evaluated by assessing the levels of PTEN-induced putative kinase 1 (PINK1) and Parkin RBR E3 ubiquitin-protein ligase (Parkin), measuring reactive oxygen species (ROS) production, and determining the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Furthermore, the mechanisms underlying the protective effects of MYR were explored.Results:MYR treatment reduced the expression of PINK1 and Parkin in TMAO-treated HUVECs, thereby attenuating mitochondrial damage and lowering ROS levels, underscoring the role of MYR in preserving mitochondrial integrity. Moreover, MYR suppressed COX-2 and iNOS expression in TMAO-treated HUVECs, reduced ROS and malondialdehyde (MDA) levels, and increased reduced glutathione (GSH) levels, indicating its ability to alleviate oxidative stress. Additionally, MYR facilitated the nuclear translocation of the nuclear factor erythroid 2–related factor 2 (NRF2) protein and upregulated the expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO-1). Notably, when NRF2 signaling was inhibited by ML385, an NRF2 signaling inhibitor, MYR no longer mitigated oxidative stress in TMAO-treated HUVECs, suggesting that its antioxidant effects are mediated by the NRF2 signaling pathway.Conclusion:These findings demonstrate that MYR protects against mitochondrial dysfunction and oxidative stress in HUVECs, likely through associated antioxidant properties and activation of the NRF2 signaling pathway.