Abstract
ScopeGinger is reported to be used for the prevention and treatment of cardiovascular diseases (CVD). Cholesterol efflux from macrophage foam cells is an important process in reverse cholesterol transport, whose increase may help to prevent or treat CVD. In this study, we investigated the effects of 6‐dihydroparadol from ginger on macrophage cholesterol efflux.Methods and resultsWe 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.ConclusionWe 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.
Highlights
Scope: Ginger is reported to be used for the prevention and treatment of ginger, in addition to their culinary application, have been used since ancardiovascular diseases (CVD)
We investigated the influence of four pungent compounds present in ginger (6-gingerol, 6-shogaol, 6-paradol, and 6-dihydroparadol)[16] on macrophage cholesterol efflux and pursued the cellular mode of action of the identified active compound, 6-dihydroparadol
To determine whether the increased ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) protein levels correlate with respective mRNA levels, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) experiments were performed. 6-Dihydroparadol slightly but significantly increases ABCA1 mRNA levels at 5 μm and 10 μm (Figure 5A), while it does not influence ABCG1 mRNA levels at both concentrations in cholesterol-loaded THP-1-derived macrophages compared to the solvent vehicle (Figure 5B)
Summary
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 eases (CVD), such as hypertension and atherosclerosis.[5,6] Ginger was reported to be used for the prevention of hypertension, which is supported by studies to the antiatherogenic effects of ginger. We investigated the influence of four pungent compounds present in ginger (6-gingerol, 6-shogaol, 6-paradol, and 6-dihydroparadol)[16] on macrophage cholesterol efflux and pursued the cellular mode of action of the identified active compound, 6-dihydroparadol
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