Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells

Int J Mol Med. 2017 Jun;39(6):1452-1460. doi: 10.3892/ijmm.2017.2949. Epub 2017 Apr 11.

Abstract

Allicin is considered anti-atherosclerotic due to its antioxidant and anti-inflammatory effects, which makes it an important drug for the prevention and treatment of atherosclerosis. However, the effects of allicin on foam cells are unclear. Thus, in this study, we examined the effects of allicin on lipid accumulation via peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) in THP‑1 macrophage-derived foam cells. THP‑1 cells were exposed to 100 nM phorbol myristate acetate (PMA) for 24 h, and then to oxydized low-density lipoprotein (ox-LDL; 50 mg/ml) to induce foam cell formation. The results of Oil Red O staining and high-performance liquid chromatography (HPLC) revealed showed that pre-treatment of the foam cells with allicin decreased total cholesterol, free cholesterol (FC) and cholesterol ester levels in cells, and also decreased lipid accumulation. Moreover, allicin upregulated ATP binding cassette transporter A1 (ABCA1) expression and promoted cholesterol efflux. However, these effects were significantly abolished by transfection with siRNA targeting ABCA1. Furthermore, PPARγ/LXRα signaling was activated by allicin treatment. The allicin-induced upregulation of ABCA1 expression was also abolished by PPARγ inhibitor (GW9662) and siRNA or LXRα siRNA co-treatment. Overall, our data demonstrate that the allicin-induced upregulation of ABCA1 promotes cholesterol efflux and reduces lipid accumulation via PPARγ/LXRα signaling in THP‑1 macrophage-derived foam cells.

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics*
  • ATP Binding Cassette Transporter 1 / metabolism
  • Cell Line
  • Cholesterol / metabolism
  • Disulfides
  • Foam Cells / drug effects*
  • Foam Cells / metabolism
  • Humans
  • Lipid Metabolism / drug effects
  • Liver X Receptors / metabolism*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • PPAR gamma / metabolism*
  • RNA, Messenger / genetics
  • Signal Transduction / drug effects*
  • Sulfinic Acids / pharmacology*
  • Up-Regulation / drug effects*

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • Disulfides
  • Liver X Receptors
  • NR1H3 protein, human
  • PPAR gamma
  • RNA, Messenger
  • Sulfinic Acids
  • allicin
  • Cholesterol