Abstract
Atherosclerosis is a multifactorial vascular disease triggered by disordered lipid metabolism, characterized by chronic inflammatory injury, and initiated by endothelial dysfunction. Berberine is the main active alkaloid of the herbal medicine Coptidis Rhizoma (Huanglian). Notably, berberine has been shown to have beneficial effects against atherosclerosis. However, the mechanisms of berberine in preventing atherosclerosis are still unclear. This study is aimed at investigating the effects and mechanisms of berberine in protecting the aorta and ameliorating atherosclerosis in apolipoprotein E-deficient (ApoE−/−) mice. Here, we demonstrated that berberine reduced serum lipid levels, antagonized hepatic lipid accumulation, improved intima-media thickening, and alleviated atherosclerotic lesions in ApoE−/− mice fed a western-type diet for 12 weeks. Meanwhile, berberine reduced aortic reactive oxygen species (ROS) generation and reduced the serum levels of malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), and interleukin-6 (IL-6). In aortic ring assay, berberine restored aortic endothelium-dependent vasodilatation in vivo and in vitro. Furthermore, 4,956 proteins were identified by proteomic analysis, and 199 differentially expressed proteins regulated by berberine were found to be involved in many biological pathways, such as mitochondrial dysfunction, fatty acid β-oxidation I, and FXR/RXR activation. Summarily, these data suggested that berberine ameliorates endothelial dysfunction and protects against atherosclerosis, and thus may be a promising therapeutic candidate for atherosclerosis.
Highlights
Atherosclerosis, a progressive chronic inflammatory disease characterized by lipid deposition, smooth muscle cell proliferation, mononuclear cell infiltration, calcification, and plaque formation, usually occurs in large and mediumsized arteries and is the main cause and pathological basis of cardiovascular disease, which is the leading cause of human death, accounting for 31.5% of all deaths worldwide [1,2,3]
ApoE-/- mice fed a western-type diet for 12 weeks were used as the atherosclerosis model, and berberine was administered by oral gavage
We further investigated the pathological changes in the aortic root in ApoE-/- mice, which exhibited an obvious accumulation of lipid, plaque formation, and severe atherosclerotic lesions, suggesting successful establishment of the atherosclerosis model
Summary
Atherosclerosis, a progressive chronic inflammatory disease characterized by lipid deposition, smooth muscle cell proliferation, mononuclear cell infiltration, calcification, and plaque formation, usually occurs in large and mediumsized arteries and is the main cause and pathological basis of cardiovascular disease, which is the leading cause of human death, accounting for 31.5% of all deaths worldwide [1,2,3]. Endothelial dysfunction is an early key step in the development of atherosclerosis, initiates the progression of atherosclerosis, and is involved in plaque formation. Inflammation is involved in endothelial dysfunction, with the activation of inflammatory cells and molecules, including adhesion molecules and chemokines [8]. When the endothelium is injured, it stimulates the expression of inflammatory mediators, including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), which activate oxidative stress and the inflammatory response and induce vascular smooth muscle cell proliferation and foam cell formation, leading to plaque formation and eventually atherosclerotic lesions [9, 10]
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