Anti-atherosclerotic effect of alfalfa flavonoid extract by regulating inflammation and oxidative stress in HUVEC cells and rats

[Display omitted] •AFE reduced inflammation in LPS-stimulated HUVEC cells and HFD-fed rats.•AFE inhibited the activities of NF-κB and MAPK signaling pathway.•AFE alleviated liver steatosis and aortic endothelium lesions in HFD-fed rats.•AFE ameliorated lipid profiles in HFD-fed rats via regulating lipid metabolism and uptake. Atherosclerosis is characterized by accumulation of lipid that triggers arterial inflammation. This study aims to investigate the protective effect of alfalfa flavonoid extract (AFE) on HUVEC cells treated with lipopolysaccharide (LPS) and rats fed with high-fat diet (HFD). AFE reduced the expression of proinflammatory factors (COX-2, iNOS, IL-1β, IL-6 and TNF-α), intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and inhibited activation of NF-κB and MAPK pathways. AFE alleviated vascular endothelial lesions by reducing HFD-enhanced levels of triglyceride, total cholesterol and low-density lipoprotein but increased high-density lipoprotein. Mechanically, AFE ameliorated HFD-enhanced liver steatosis through downregulating gene expression for lipid biosynthesis (SREBP2, HMGCR and FASN) and lipid uptake (LDLR), and through upregulating CYP7A1 expression for lipid catabolism and excretion. These data suggest that AFE possesses the anti-atherosclerotic potential through controlling inflammation, hyperlipidemia and lipid metabolism, and can be used as a functional food additive to benefit patients with atherosclerosis.