Myricetin ameliorates atherosclerosis in the low-density-lipoprotein receptor knockout mice by suppression of cholestero

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Myricetin ameliorates atherosclerosis in the low-density-lipoprotein receptor knockout mice by suppression of cholesterol accumulation in macrophage foam cells Zhe Meng†, Mengyu Wang†, Junhui Xing, Yuzhou Liu and Haiyu Li*

Abstract Background: 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 (Ldlr−/−) mice. Methods: Ldlr−/− mice were fed an atherogenic diet supplemented with myricetin (0.15% in the diet, v/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. Results: Myricetin administration reduced the weight, plasma lipid levels but not food intake in Ldlr−/− mice when fed an atherogenic diet. Myceritin-treated Ldlr−/− mice displayed significantly less atherosclerotic areas and macrophages in the cross sections of the aortic root. There were also less lipophilic areas in En face Oil red O staining of aorta from myceritin-treated Ldlr−/− mice. Myceritin treatment also markedly ameliorated oxLDL-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. Conclusions: 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. Keywords: Myricetin, Macrophage, Atherosclerosis, CD36

* Correspondence: [email protected] † Zhe Meng and Mengyu Wang contributed equally to this work and co-first authors. Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Cr