Luteolin decreases atherosclerosis in LDL receptor-deficient mice via a mechanism including decreasing AMPK-SIRT1 signaling in macrophages.

Lipid metabolism dysfunction and inflammatory infiltration into arterial walls are associated with the initiation and progression of atherosclerosis. Luteolin has been reported to possess anti-inflammatory actions and protect against tumor necrosis factor-α (TNF-α)-induced vascular inflammation, monocyte adhesion to endothelial cells and the formation of lipid-laden macrophages in vitro. However, the role of luteolin in atherosclerosis and the associated vascular inflammatory remains to be elucidated. The aim of the present study was to investigate the effects of luteolin on plaque development, lipid accumulation and macrophage inflammation low-density lipoprotein receptor-deficient (LDLR-/-) mice with atherosclerosis, as well as the underlying mechanisms in ox-induced THP-1-derived macrophages. Firstly, 9-week-old male C57BL/6 mice were fed a standard chow diet, western diet or western diet supplemented with 100 mg/kg luteolin for 14 weeks. The results of histological staining revealed that 100 mg/kg dietary luteolin ameliorated western diet-induced atherosclerotic plaque development and lipid accumulation in the abdominal aorta. Furthermore, total cholesterol, triglyceride and LDL-cholesterol levels were decreased in the plasma of western diet + luteolin mice compared with those fed with a western diet alone. Quantitative polymerase chain reaction analysis revealed that dietary luteolin inhibited the expression of cluster of differentiation 68, macrophage chemoattractant protein 2 and inflammatory cytokines, including interleukin-6 (IL-6) and TNF-α. Mechanistically, luteolin decreased the total cholesterol level as well as macrophage chemokine and inflammatory cytokine expression in THP-1-derived macrophages via AMP-activated protein kinase (AMPK)-Sirtuin (SIRT)1 signaling following induction with oxidized low-density lipoprotein. The results of the present study suggest that luteolin prevents plaque development and lipid accumulation in the abdominal aorta by decreasing macrophage inflammation during atherosclerosis, which is mediated by mechanisms including AMPK-SIRT1 signaling.