Rutaecarpine suppresses atherosclerosis in ApoE-/- mice through upregulating ABCA1 and SR-BI within RCT.

ABCA1 and scavenger receptor class B type I (SR- BI)/CD36 and lysosomal integral membrane protein II analo- gous 1 (CLA-1) are the key transporter and receptor in reverse cholesterol transport (RCT). Increasing the expression level of ABCA1 and SR-BI/CLA-1 is antiatherogenic. The aim of the study was to fi nd novel antiatherosclerotic agents upregulating expression of ABCA1 and SR-BI/CLA-1 from natural com- pounds. Using the ABCA1p-LUC and CLA-1p-LUC HepG2 cell lines, we found that rutaecarpine (RUT) triggered promot- ers of ABCA1 and CLA-1 genes. RUT increased ABCA1 and SR-BI/CLA-1 expression in vitro related to liver X receptor al- pha and liver X receptor beta. RUT induced cholesterol effl ux in RAW264.7 cells. ApoE-defi cient (ApoE � / � ) mice treated with RUT for 8 weeks showed 68.43, 70.23, and 85.56% less en face lesions for RUT (L), RUT (M), and RUT (H) groups, respectively, compared with the model group. Mouse macro- phage-specifi c antibody and fi lipin staining indicated that RUT attenuated macrophages and cholesterol accumulations in ath- erosclerotic lesions, respectively. Additionally, ABCA1 and SR- BI expression was highly induced by RUT in livers of ApoE � / �