PMID- 29802792 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240330 IS - 1613-4133 (Electronic) IS - 1613-4125 (Print) IS - 1613-4125 (Linking) VI - 62 IP - 14 DP - 2018 Jul TI - 6-Dihydroparadol, a Ginger Constituent, Enhances Cholesterol Efflux from THP-1-Derived Macrophages. PG - e1800011 LID - 10.1002/mnfr.201800011 [doi] LID - 1800011 AB - SCOPE: Ginger 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 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. 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. CI - (c) 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Wang, Dongdong AU - Wang D AD - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria. AD - Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, ul. Postepu 36A, 05-552, Jastrzebiec, Poland. AD - Institute of Clinical Chemistry, University Hospital Zurich, University of Zurich, Wagistrasse 14, 8952, Schlieren, Switzerland. FAU - Hiebl, Verena AU - Hiebl V AD - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria. FAU - Ladurner, Angela AU - Ladurner A AD - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria. FAU - Latkolik, Simone L AU - Latkolik SL AD - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria. FAU - Bucar, Franz AU - Bucar F AD - Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, 8010, Graz, Austria. FAU - Heiss, Elke H AU - Heiss EH AD - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria. FAU - Dirsch, Verena M AU - Dirsch VM AD - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria. FAU - Atanasov, Atanas G AU - Atanasov AG AUID- ORCID: 0000-0003-2545-0967 AD - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria. AD - Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, ul. Postepu 36A, 05-552, Jastrzebiec, Poland. LA - eng GR - P 25971/FWF_/Austrian Science Fund FWF/Austria GR - H-297332/2014/Vienna Anniversary Foundation for Higher Education (Hochschuljubilaumsstiftung der Stadt Wien)/ GR - GZ402.000/00014-WF/V/6/2016/Austrian Federal Ministry of Science, Research and Economy/ GR - European Regional Development Fund/ GR - 05-1/KNOW2/2015/Ministry of Science and Higher Education/ GR - P25971-B23/Austrian Science Fund/ PT - Journal Article DEP - 20180625 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 SB - IM PMC - PMC6099374 MID - EMS78584 OTO - NOTNLM OT - ATP-binding cassette transporter A1 OT - ATP-binding cassette transporter G1 OT - atherosclerosis OT - cardiovascular diseases OT - cholesterol efflux EDAT- 2018/05/29 06:00 MHDA- 2018/05/29 06:01 PMCR- 2018/08/20 CRDT- 2018/05/27 06:00 PHST- 2018/04/24 00:00 [revised] PHST- 2018/01/05 00:00 [received] PHST- 2018/05/29 06:00 [pubmed] PHST- 2018/05/29 06:01 [medline] PHST- 2018/05/27 06:00 [entrez] PHST- 2018/08/20 00:00 [pmc-release] AID - MNFR3246 [pii] AID - 10.1002/mnfr.201800011 [doi] PST - ppublish SO - Mol Nutr Food Res. 2018 Jul;62(14):e1800011. doi: 10.1002/mnfr.201800011. Epub 2018 Jun 25.