Sweroside Inhibits Inflammation and Alleviates Endothelial Injury and Atherosclerosis in Mice

Abstract

The underlying mechanisms in atherosclerotic vascular diseases are not entirely clear, posing a challenging hurdle to treatment. Inflammation is a root cause of atherosclerosis (AS); therefore, anti-inflammatory agents have potential for its management. Sweroside, possessing anti-inflammatory properties, emerges as a potential agent to impede AS progression. In this study, we investigated the effects of sweroside on AS mice and elucidated its molecular mechanisms. We conducted in vivo experiments using an apolipoprotein E mice model of AS to explore the effects of sweroside on vascular inflammation adhesion responses, endothelial injury and AS. In vitro experiments, mouse aorta endothelial cells were treated with palmitic acid (PA) and sweroside, and the protective effects of sweroside on endothelial injury were analysed. AS is a chronic inflammatory disease and activation of nuclear factor κB (NF-κB) signalling contributes to inflammatory reactions and AS. Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) has been identified as an upstream target of NF-κB signalling. We detected MAP4K4/NF-κB signalling pathways using gene siRNA silencing and knockdown assays and investigated the protective effects of sweroside in PA-mediated endothelial injury and western-diet-induced AS. The findings demonstrated that sweroside attenuated vascular inflammation, adhesion responses, and leukocyte homing and alleviated endothelial injury and atherosclerosis in vivo. Sweroside attenuated endothelial inflammation, apoptosis, permeability and adhesion responses induced by PA in vitro. Sweroside alleviated endothelial injury and atherosclerosis through MAP4K4/NF-κB signalling. Hence, sweroside is a promising candidate for treating AS, acting by targeting the MAP4K4/NF-κB pathway.