Huang Minjiang, Yin Huiming, Yang Qiansheng, Liu Lingli, Chen Yuefu, Jin Ling, Yang Yang, Hu Ke, Ding Yan
Department of Diagnostics, Hunan University of Medicine, Huaihua, Hunan, China.
Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Hunan University of Medicine, Huaihua, Hunan, China.
J Cell Mol Med. 2025 Sep;29(17):e70837. doi: 10.1111/jcmm.70837.
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.
动脉粥样硬化性血管疾病的潜在机制尚不完全清楚，这给治疗带来了挑战性障碍。炎症是动脉粥样硬化（AS）的根本原因；因此，抗炎药物具有治疗AS的潜力。獐牙菜苷具有抗炎特性，是一种潜在的阻碍AS进展的药物。在本研究中，我们研究了獐牙菜苷对AS小鼠的影响，并阐明了其分子机制。我们使用AS的载脂蛋白E小鼠模型进行体内实验，以探索獐牙菜苷对血管炎症黏附反应、内皮损伤和AS的影响。在体外实验中，用棕榈酸（PA）和獐牙菜苷处理小鼠主动脉内皮细胞，并分析獐牙菜苷对内皮损伤的保护作用。AS是一种慢性炎症性疾病，核因子κB（NF-κB）信号通路的激活促进炎症反应和AS。丝裂原活化蛋白激酶激酶激酶激酶4（MAP4K4）已被确定为NF-κB信号通路的上游靶点。我们使用基因siRNA沉默和敲低实验检测MAP4K4/NF-κB信号通路，并研究獐牙菜苷在PA介导的内皮损伤和西式饮食诱导的AS中的保护作用。研究结果表明，獐牙菜苷在体内可减轻血管炎症、黏附反应和白细胞归巢，并减轻内皮损伤和动脉粥样硬化。在体外，獐牙菜苷可减轻PA诱导的内皮炎症、凋亡、通透性和黏附反应。獐牙菜苷通过MAP4K4/NF-κB信号通路减轻内皮损伤和动脉粥样硬化。因此，獐牙菜苷是一种有前途的治疗AS的候选药物，其作用靶点为MAP4K4/NF-κB通路。
