低密度脂蛋白受体
表皮生长因子受体
MAPK/ERK通路
信号转导
鞣花酸
化学
低密度脂蛋白
癌症研究
表皮生长因子
受体
脂蛋白
药理学
细胞外
胆固醇
细胞生物学
生物
生物化学
抗氧化剂
多酚
作者
Yewei Huang,Litian Wang,Huaxiang Yin,Dandan Hu,Jun Sheng,Xuanjun Wang
标识
DOI:10.1101/2023.09.14.557846
摘要
BACKGROUND High levels of plasma low-density lipoprotein (LDL) are a key risk factor for atherosclerosis. Low-density lipoprotein receptor (LDLR) mediates the degradation of plasma LDL. Therefore, it may be possible to prevent and treat atherosclerosis by increasing the levels of LDLR. The natural polyphenolic compound ellagic acid (EA) has various biological activities. In mice, EA alleviated the progression of atherosclerosis; however, the underlying mechanism remains unclear. METHODS Molecular interaction, cell, and animal experiments were used to explore the role and mechanism of EA in improving atherosclerosis. RESULTS EA binds to the extracellular domain of the epidermal growth factor receptor (EGFR), thus activating the EGFR-extracellular signal-regulated kinase (EGFR-ERK) signaling pathway, stabilizing LDLR mRNA, and promoting the expression of LDLR protein. The development of EA-loaded human serum albumin nanoparticles enabled intravenous administration in animal experiments. CONCLUSIONS The research verified the in vivo effects of EA on the EGFR-ERK signaling pathway, LDLR levels, and atherosclerosis. EA may assist in the prevention and treatment of atherosclerosis.
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