Astragalin Retards Atherosclerosis by Promoting Cholesterol Efflux and Inhibiting the Inflammatory Response via Upregulating ABCA1 and ABCG1 Expression in Macrophages
Authors: Xiao-Hua Yu
Gang Wang
Chao-Ke Tang
Min Zhang
Li Zhou
Da-Wei Zhang
Jin Zou
Zhen-Wang Zhao
Jia-Hui Gao
Xiang-Jun Wan
Journal: Journal of Cardiovascular Pharmacology (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Lipid metabolism disorder; inflammatory response; atherosclerogenesis; astragalin; flavonoid
Affiliations: Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Medical Research Experiment Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, China., Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada and., Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.

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. 

Retracted: No

PubPeer comments:
 1. Base-editing will have too many [off-targets] 2. dCas9 still has residual endonuclease (will result in [plasmid integration] ). And the same happens here. Here are [100 s such sequences] , which integrate the plasmid to the human mice genome. As a specific eg, see this [sample] - where the DNMT gene was edited using CBE (Fig4c_PHPB-v5CBE_DNMT1-Cortex-unsorted_Rep1). The Cas9 integrates with the DNMT1 gene. One cant ask for better proof. SRR10591680.78397.1 78397 length=176 AAAGGCCGGGGTCTCGTTCAGAGCTGTTCTGTCGTCTGCAACCTGCAAGATGCCAGCGCTAGAATGCTG GCCTCTGCCGGCGAACTGCAGAAGGGAAACGAACTGGCCCTGCCCTCCAAGTGCCTGCGCTTGCCTCCC CGGCAGGCTCGCTCCCGGACCATGTCCGCAGGCGGTAG ![file] , 
 Is there not a single scientist worth her his salt who questions these Harvard MIT ... high priests of science? They say [dCas9 or Prime-editing (nickases)] has no double stranded breaks, and you believe it blindly? While data screams out - NO ! ,