Myricetin ameliorates atherosclerosis in the low-density-lipoprotein receptor knockout mice by suppression of cholesterol accumulation in macrophage foam cells

• Published in: Nutrition & metabolism Vol. 16; no. 1; p. 25
• Main Authors: Meng, Zhe, Wang, Mengyu, Xing, Junhui, Liu, Yuzhou, Li, Haiyu
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.04.2019; BioMed Central; BMC
• Subjects: Adipose tissue; Antioxidants; Antioxidants (Nutrients); Aorta; Arteriosclerosis; Atherogenic diet; Atherosclerosis; Biochemistry; Body weight; CD36; CD36 antigen; Cholesterol; Coronary vessels; Flavonoids; Flow cytometry; Food intake; Fruits; Gene expression; Grapes; Lipid metabolism; Lipids; Lipophilic; Low density lipoprotein; Low density lipoprotein receptors; Low density lipoproteins; Macrophage; Macrophages; Messenger RNA; Metabolism; Metabolites; Microscopy; Myricetin; Obesity; Physiological aspects; Protein turnover; Receptor density; Risk factors; RNA; Rodents; Scavenger receptors; Sinuses; Wine; United States > US; CD36; Myricetin; Atherosclerosis; Macrophage
• ISSN: 1743-7075; 1743-7075
• DOI: 10.1186/s12986-019-0354-7

Myricetin, a major flavonoid found in several foods including berries, grapes and wine, exhibited strong antioxidant potency, yet the effect on atherosclerosis is not fully understood. In this study, we examined the effect of myricetin on lipid accumulation in macrophage and atherosclerosis in atherosclerosis-prone low density lipoprotein receptor-deficient ( ) mice. mice were fed an atherogenic diet supplemented with myricetin (0.15% in the diet, /v) for 8 weeks. Body weight, adipose tissue weight, food intake, serum biochemical parameters were measured. Atherosclerosis lesions and macrophages accumulaton in lesions were analyzed and quantified. Macrophages were exposed to 20 μM of myricetin before incubated with oxidized low-density lipoprotein (ox-LDL) (25μg/mL) or Dil-ox-LDL for the indicated time. Lipid uptake and foam cell formation were evaluated by flow cytometry and microscopy. The intracellular lipids were extracted and measured. mRNA expression and protein of cholesterol metabolism related receptors were analyzed. Myricetin administration reduced the weight, plasma lipid levels but not food intake in mice when fed an atherogenic diet. Myceritin-treated mice displayed significantly less atherosclerotic areas and macrophages in the cross sections of the aortic root. There were also less lipophilic areas in Oil red O staining of aorta from myceritin-treated mice. Myceritin treatment also markedly ameliorated ox-LDL-induced cholesterol accumulation in macrophages. The expression of CD36 were decreased in myricetin treated macrophages with ox-LDL incubation, while scavenger receptors class A (SR-A) and scavenger receptors class B (SR-BI) expression was not altered, indicating that these effect of myricetin were dependent on CD36 pathway. Our findings indicated that myricetin suppressed cholesterol accumulation in macrophage foam cells by inhibition of CD36-mediated ox-LDL uptake, and suggested myricetin may have an important therapeutic function for atherosclerosis.