Curcumin increases cholesterol efflux via hemeoxygenase-1-mediated ABCA1 and SR-BI expression in macrophages

Abstract

Curcumin, which is an extract from a traditional Chinese medicine, has previously been demonstrated to exhibit an anti-atherosclerotic effect, which is closely associated with an increase in cholesterol efflux. However, it is unclear as to whether the increased effect is mediated by heme oxygenase (HO)-1. Macrophages were treated with different concentrations of curcumin, HO-1 inhibitor and small interfering (si)RNA in different experiments. Analysis of protein expression was conducted via western blotting. mRNA expression levels were measured using reverse transcription-polymerase chain reaction. Antioxidant response element (ARE)-driven promoter activity was measured by a dual-luciferase reporter assay. The cholesterol efflux analysis was performed by fluorescence-labelled cholesterol (NBD) using a multi-label counter. In the present study, the results indicated that curcumin increased the cholesterol efflux from macrophages. Additionally, curcumin significantly upregulated HO-1 expression. The HO-1 inhibitor (zinc protoporphyrin) partly blocked this effect. Curcumin also promoted scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter A1 (ABCA1) expression. HO-1 small interfering (si)RNA partly abolished the increased SR-BI and ABCA1 expression induced by curcumin. Furthermore, the nuclear factor, erythroid 2 like 2 (Nrf2) expression in the nucleus was dose-dependently increased by curcumin. Nrf2 siRNA successfully inhibited the curcumin-induced HO-1 expression. Curcumin significantly increased Nrf2-driven luciferase activity. Overall, these data indicated that curcumin activates the Nrf2-ARE signaling pathway and upregulates HO-1 expression, which mediates SR-BI and ABCA1 expression and thereby increases cholesterol efflux.