Molecules 2012, 17(3), 2833-2854; doi:10.3390/molecules17032833
Article

IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1

Received: 1 December 2011; in revised form: 16 February 2012 / Accepted: 24 February 2012 / Published: 7 March 2012
(This article belongs to the collection Bioactive Compounds)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: It is known that the ATP-binding cassette transporter A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein (HDL) metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I) will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS) method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO) cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein) expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791) was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell) further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC50 of 25.23 μM.
Keywords: ABCA1; regulator; high-throughput screening; xanthone; anti-atherosclerosis agent; cholesterol efflux
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MDPI and ACS Style

Liu, J.; Zhang, Z.; Xu, Y.; Feng, T.; Jiang, W.; Li, Z.; Hong, B.; Xie, Z.; Si, S. IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1. Molecules 2012, 17, 2833-2854.

AMA Style

Liu J, Zhang Z, Xu Y, Feng T, Jiang W, Li Z, Hong B, Xie Z, Si S. IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1. Molecules. 2012; 17(3):2833-2854.

Chicago/Turabian Style

Liu, Jikai; Zhang, Zhongbing; Xu, Yanni; Feng, Tingting; Jiang, Wei; Li, Zhuorong; Hong, Bin; Xie, Zijian; Si, Shuyi. 2012. "IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1." Molecules 17, no. 3: 2833-2854.

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