Emodin enhances cholesterol efflux by activating peroxisome proliferator-activated receptor-γ in oxidized low density lipoprotein-loaded THP1 macrophages.

Peroxisome proliferator-activated receptor (PPAR) γ is a nuclear receptor involved in the regulation of lipid metabolism. In the present study, we sought to investigate the effects of emodin, an anthraquinone derivative isolated from the roots of Rheum palmatum, on PPARγ signalling and cholesterol efflux in macrophage foam cells. Oxidized low-density lipoprotein (oxLDL)-stimulated THP1 macrophages were incubated with different concentrations of emodin (0-10 μmol/L) for 18 h. Western blot analysis and semiquantitative reverse transcription-polymerase chain reaction were used to assess the expression of key genes involved in cholesterol efflux, namely PPARγ, liver X receptor (LXR) α, ATP-binding cassette transporter (ABC) A1 and ABCG1. In addition, apolipoprotein (apo) A-I-mediated cholesterol efflux in emodin-treated cells was measured. Expresssion of PPARγ mRNA and protein was increased in emodin-treated cells in a time- and dose-dependent manner. Emodin treatment also concentration-dependently induced LXRα, ABCA1 and ABCG1 expression. Moreover, emodin promoted apoA-I-mediated cholesterol efflux from oxLDL-loaded THP1 macrophages, which was significantly abolished by pretreatment with the PPARγ-selective antagonist GW9662 or the specific small interfering RNA for PPARγ. Together, the results demonstrate that emodin promotes cholesterol efflux from THP1 macrophages via activation of the PPARγ signalling pathway and may represent a potential anti-atherosclerotic drug.