Curcumin increases cholesterol efflux via heme oxygenase‑1‑mediated ABCA1 and SR‑BI expression in macrophages

Zhong,Yi; Feng,Jian; Fan,Zhongcai; Li,Jiafu

doi:10.3892/mmr.2018.8577

Curcumin increases cholesterol efflux via heme oxygenase‑1‑mediated ABCA1 and SR‑BI expression in macrophages

Authors:
- Yi Zhong
- Jian Feng
- Zhongcai Fan
- Jiafu Li
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Affiliations: Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: February 8, 2018 https://doi.org/10.3892/mmr.2018.8577
Pages: 6138-6143

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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.

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