Ginger is reported to be used for the prevention and treatment of cardiovascular diseases (CVD) [1, 2] . Cholesterol efflux from macrophage foam cells is an important process in reverse cholesterol transport, whose increase may help to prevent or treat CVD [3]. In this study, we investigated the effects of 6-dihydroparadol, a ginger constituent, on macrophage cholesterol efflux. We show that 6-dihydroparadol enhances concentration-dependently both apolipoprotein A1- and human plasma-mediated cholesterol efflux from cholesterol-loaded THP-1-derived macrophages. 6-Dihydroparadol increases protein levels of both ATP-binding cassette transporter A1 and G1 (ABCA1 and ABCG1) according to Western blot analysis. Application of probucol (ABCA1 inhibitor) revealed that the 6-dihydroparadol-promoted efflux mainly correlates with increased ABCA1 protein levels. Application of probucol (ABCA1 inhibitor) revealed that the 6-dihydroparadol-promoted efflux mainly correlates with increased ABCA1 protein levels. Furthermore, increased ABCA1 protein levels in the presence of 6-dihydroparadol were associated with both increased ABCA1 mRNA levels and increased ABCA1 protein stability. Enhanced ABCG1 protein levels were only associated with increased protein stability. Increased ABCA1 protein stability appeared to be the result of a reduced proteasomal degradation of the transporter in the presence of 6-dihydroparadol. We identified 6-dihydroparadol, a ginger constituent, as a novel promoter of cholesterol efflux from macrophages that increases both ABCA1 and ABCG1 protein abundance. This newly identified bioactivity might contribute to the antiatherogenic effects of ginger.
[1] Kim HJ, et al. J Cell Biochem 2018; 119(1): 260-268.
[2] Wang J, Ke W, Bao R, Hu X, Chen F. Ann N Y Acad Sci 2017; 1398(1): 83-98.
[3] Rohatgi A, et al. N Engl J Med 2014; 371(25): 2383-2393.