Conclusion
We identified 6-dihydroparadol from ginger 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.
Results
We show that 6-dihydroparadol concentration-dependently enhances both apolipoprotein A1- and human plasma-mediated cholesterol efflux from cholesterol-loaded THP-1-derived macrophages using macrophage cholesterol efflux assay. 6-Dihydroparadol increases protein levels of both ATP-binding cassette transporters A1 and G1 (ATP-binding cassette transporter A1 [ABCA1] and ATP-binding cassette transporter G1 [ABCG1]) according to Western blot analysis. The ABCA1 inhibitor probucol completely abolishes 6-dihydroparadol-enhanced cholesterol efflux. 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.