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Leoligin, the Major Lignan from Edelweiss (Leontopodium nivale subsp. alpinum), Promotes Cholesterol Efflux from THP-1 Macrophages

Author:
Wang, Limei, Ladurner, Angela, Latkolik, Simone, Schwaiger, Stefan, Linder, Thomas, Hošek, Jan, Palme, Veronika, Schilcher, Nicole, Polanský, Ondřej, Heiss, Elke H., Stangl, Herbert, Mihovilovic, Marko D., Stuppner, Hermann, Dirsch, Verena M., Atanasov, Atanas G.
Source:
Journal of natural products 2016 v.79 no.6 pp. 1651-1657
ISSN:
1520-6025
Subject:
mechanism of action, messenger RNA, protein synthesis, proteome, atherosclerosis, cell viability, Leontopodium nivale, actinomycin D, humans, transporters, macrophages, polymerase chain reaction, Western blotting, cholesterol, transcription (genetics), lignans, half life
Abstract:
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.
Agid:
5498555