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Astragalin Retards Atherosclerosis by Promoting Cholesterol Efflux and Inhibiting the Inflammatory Response via Upregulating ABCA1 and ABCG1 Expression in Macrophages.

Authors :
Zhao ZW
Zhang M
Wang G
Zou J
Gao JH
Zhou L
Wan XJ
Zhang DW
Yu XH
Tang CK
Source :
Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 2021 Feb 01; Vol. 77 (2), pp. 217-227.
Publication Year :
2021

Abstract

Abstract: Lipid metabolism disorder and inflammatory response are considered to be the major causes of atherosclerogenesis. Astragalin, the most important functional component of flavonoid obtained from persimmon leaves, has the hypolipidemic effects. However, it is unknown, how astragalin protects against atherosclerosis. The aim of this study was to observe the effects of astragalin on cholesterol efflux and inflammatory response and to explore the underlying mechanisms. Our results showed that astragalin upregulated the expression of ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1), promoted cholesterol efflux, and suppressed foam cell formation. Inhibition of the PPARγ/LXRα pathway abrogated the promotive effects of astragalin on both transporter expression and cholesterol efflux. In addition, treatment of astragalin markedly decreased the secretion of inflammatory factors, including interleukin 6, monocyte chemotactic protein 1, tumor necrosis factor α, and interleukin 1β. Mechanistically, astragalin upregulated ABCA1 and ABCG1 expression, which in turn reduced TLR4 surface levels and inhibited NF-κB nuclear translocation. Consistently, astragalin reduced atherosclerotic plaque area in apoE-/- mice. Taken together, these findings suggest that astragalin protects against atherosclerosis by promoting ABCA1- and ABCG1-mediated cholesterol efflux and inhibiting proinflammatory mediator release.<br />Competing Interests: The authors report no conflicts of interest.<br /> (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Details

Language :
English
ISSN :
1533-4023
Volume :
77
Issue :
2
Database :
MEDLINE
Journal :
Journal of cardiovascular pharmacology
Publication Type :
Academic Journal
Accession number :
33165140
Full Text :
https://doi.org/10.1097/FJC.0000000000000944