A Novel Peptide Isolated from Microalgae Isochrysis zhanjiangensis Exhibits Anti-apoptosis and Anti-inflammation in Ox-LDL Induced HUVEC to Improve Atherosclerosis

In the early stage, oxidized low density lipoprotein (ox-LDL) caused atherosclerosis, followed by human umbilical vein endothelial cells (HUVEC) damage, leading to a variety of cardiovascular related diseases. This study investigated the mechanism of nonapeptide (EMFGTSSET, ETT) isolated from in vitro gastrointestinal digestion of Isochrysis zhanjiang on endothelial cell inflammation and apoptosis induced by ox-LDL in atherosclerosis. At the cellular level, the results shown that ETT inhibited the up-regulation of oxidized low-density lipoprotein receptor-1 (LOX-1) induced by ox-LDL. Furthermore, ETT inhibited the fluorescence intensity of ROS, inflammatory factors (interleukin-6, interleukin-1β, and tumor necrosis factor-α) and the expression of cell adhesion molecules (vascular cell adhesion protein 1 and intercellular cell adhesion molecule-1). In addition, it also upregulates nuclear red blood cell 2 related factor 2 (Nrf2), heme oxygenase-1 (HO -1), p-Akt, and bcl-2 levels. But down-regulated the expression of p-p65, p-IκB-α, p-p38, p-ERK, p-JNK, bax, and cleaved caspase-9/-3 (c-c-9/-3), thereby inhibited ox-LDL induction inflammation and apoptosis of atherosclerosis. Through molecular docking, it was judged that the stable interaction between ETT and LOX-1 and VCAM-1 was maintained through hydrogen bonding. These results can provide a theoretical basis for ETT as a potential substance for the prevention and treatment of atherosclerosis, and further improve the value of Isochrysis zhanjiangensis.