Leoligin, the Major Lignan from Edelweiss (Leontopodium nivale subsp. alpinum), Promotes Cholesterol Efflux from THP-1 Macrophages
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27220065
PubMed Central
PMC4924082
DOI
10.1021/acs.jnatprod.6b00227
Knihovny.cz E-resources
- MeSH
- ATP-Binding Cassette Transporters metabolism MeSH
- Asteraceae chemistry MeSH
- Atherosclerosis MeSH
- Biological Transport MeSH
- Dactinomycin pharmacology MeSH
- Humans MeSH
- Lignans chemistry isolation & purification pharmacology MeSH
- Macrophages metabolism MeSH
- RNA, Messenger metabolism MeSH
- Molecular Structure MeSH
- Oxazines metabolism MeSH
- Polymerase Chain Reaction MeSH
- Orphan Nuclear Receptors metabolism MeSH
- Blotting, Western MeSH
- Xanthenes metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ATP-Binding Cassette Transporters MeSH
- Dactinomycin MeSH
- leoligin MeSH Browser
- Lignans MeSH
- RNA, Messenger MeSH
- Oxazines MeSH
- resazurin MeSH Browser
- Orphan Nuclear Receptors MeSH
- Xanthenes MeSH
Leoligin is a natural lignan found in Edelweiss (Leontopodium nivale ssp. alpinum). The aim of this study was to examine its influence on cholesterol efflux and to address the underlying mechanism of action. Leoligin increases apo A1- as well as 1% human plasma-mediated cholesterol efflux in THP-1 macrophages without affecting cell viability as determined by resazurin conversion. Western blot analysis revealed that the protein levels of the cholesterol efflux transporters ABCA1 and ABCG1 were upregulated, whereas the SR-B1 protein level remained unchanged upon treatment with leoligin (10 μM, 24 h). Quantitative reverse transcription PCR further uncovered that leoligin also increased ABCA1 and ABCG1 mRNA levels without affecting the half-life of the two mRNAs in the presence of actinomycin D, a transcription inhibitor. Proteome analysis revealed the modulation of protein expression fingerprint in the presence of leoligin. Taken together, these results suggest that leoligin induces cholesterol efflux in THP-1-derived macrophages by upregulating ABCA1 and ABCG1 expression. This novel activity suggests leoligin as a promising candidate for further studies addressing a possible preventive or therapeutic application in the context of atherosclerosis.
Department of Pharmacognosy University of Vienna Vienna Austria
Institute of Applied Synthetic Chemistry Vienna University of Technology Vienna Austria
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