The in vitro anti-atherosclerotic activity of compound E0869.
- Author:
Xiao WANG
;
Chang LIU
;
Peng LIU
;
Ni LI
;
Yan-Ni XU
;
Shu-Yi SI
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter 1;
metabolism;
Animals;
Atherosclerosis;
drug therapy;
Biological Transport;
Cholesterol;
Hep G2 Cells;
High-Throughput Screening Assays;
Humans;
Macrophages, Peritoneal;
drug effects;
Mice;
RNA, Messenger;
Scavenger Receptors, Class B;
metabolism;
Up-Regulation
- From:
Acta Pharmaceutica Sinica
2015;50(4):440-446
- CountryChina
- Language:Chinese
-
Abstract:
ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI/CLA-1) are the key proteins in reverse cholesterol transport (RCT). The high expression of ABCA1 and SR-BI/CLA-1 can decrease the danger of atherosclerosis. The purpose of the study is to find ABCA1 and CLA-1up-regulators for treating atherosclerosis by using cell-based high throughput screening models. Among 20 000 compounds screened, E0869 [1-(3, 4-dimethylphenyl)-1-oxopropan-2-yll4-((methylsulfonyl)methyl)benzoate] was found as the positive hit. The up-regulated activities of E0869 in ABCAl1-LUC and bCA-l1-LUC HepG2 cell were 160% and 175%, respectively. The EC50 values of E0869 in ABCAl1-LUC and CLA-l1-LUC HepG2 cell were 3.79 and 1.42 pμol- x ,(-1) respectively. E0869 could upregulate the mRNA and protein levels of ABCA1, SR-BI/CLA-1 and ABCGJ1genes in HepG2 and RAW264.7 cells by Real-Time Quantitative PCR and Western blotting analysis, but could not influence the expression of FAS, SREBP-l1 and CD36. Foam cell assay showed that E0869 could inhibit lipids accumulation in mouse peritoneal macrophages RAW264.7. Cholesterol efflux assay showed that E0869 could induce HDL-mediated cholesterol efflux in mouse peritoneal macrophages RAW264.7. In conclusion, E0869 could up-regulate ABCA1 and CLA-1 activity, and had good anti-atherosclerotic activity in vitro.
