In vitro effect and mechanistic study of compound E23869 on lipid metabolism
10.16438/j.0513-4870.2015-0826
- VernacularTitle:E23869体外对脂代谢的调节作用及机制研究
- Author:
Shuang-shuang YANG
1
;
Yan-ni XU
2
;
Peng LIU
2
;
Xiao WANG
2
;
Xiao-wan HAN
2
;
Zhuo-wen FAN
1
;
Shu-yi SI
2
Author Information
1. Heilongjiang University of Chinese Medicine, Harbin 150040, China
2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
ATP-binding cassette transporter A1;
scavenger receptor class B type I;
ATP-binding cassette transporter G1;
peroxisome proliferator-activated receptor;
lipid metabolism
- From:
Acta Pharmaceutica Sinica
2016;51(4):563-
- CountryChina
- Language:Chinese
-
Abstract:
This study was designed to identify inducers of ATP-binding cassette transporter A1(ABCA1) and CD36 and lysosomal integral membrane protein-II analogous-1(CLA-1) and to evaluate the in vitro effect of the active compound on lipid metabolism. Among 20000 compounds screened, E23869 was found as a positive hit using cell-based high throughput screening models. The up-regulating activities of E23869 in ABCA1p-LUC and CLA-1p-LUC HepG2 cells were 196% and 198%, respectively. The EC50 values of E23869 in ABCA1p-LUC and CLA-1p-LUC HepG2 cells were 0.25 μmol·L-1 and 0.66 μmol·L-1, respectively. E23869 significantly upregulated the protein levels of ABCA1, scavenger receptor class B type I (SR-BI)/CLA-1 and ATP-binding cassette transporter G1(ABCG1) in both macrophages RAW264.7 and L02 cells by Western blotting analysis. Foam cell assay showed that E23869 inhibited lipids accumulations in macrophages RAW264.7. Cholesterol efflux assay showed that E23869 induced HDL-mediated cholesterol efflux in macrophages RAW264.7. Moreover, E23869 up-regulated ABCA1, SR-BI/CLA-1 and ABCG1 expressions through activation of PPARα and PPARγ. In addition, E23869 weakly promoted in vitro differentiation of mouse preadipocytes 3T3-L1. In conclusion, E23869 up-regulated ABCA1, SR-BI/CLA-1 and ABCG1 expressions to promote cholesterol efflux, which is a good leading compound for regulation of lipid metabolism.