Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Duwensee, K; Schwaiger, S; Tancevski, I; Eller, K; van Eck, M; Markt, P; Linder, T; Stanzl, U; Ritsch, A; Patsch, JR; Schuster, D; Stuppner, H; Bernhard, D; Eller, P.
Leoligin, the major lignan from Edelweiss, activates cholesteryl ester transfer protein.
Atherosclerosis. 2011; 219(1): 109-115.
Doi: 10.1016/j.atherosclerosis.2011.07.023
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- Führende Autor*innen der Med Uni Graz
- Eller Philipp
- Co-Autor*innen der Med Uni Graz
- Eller Kathrin
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- Abstract:
- OBJECTIVE: Cholesteryl ester transfer protein (CETP) plays a central role in the metabolism of high-density lipoprotein particles. Therefore, we searched for new drugs that bind to CETP and modulate its activity. METHODS: A preliminary pharmacophore-based parallel screening approach indicated that leoligin, a major lignan of Edelweiss (Leontopodium alpinum Cass.), might bind to CETP. Therefore we incubated leoligin ex vivo at different concentrations with human (n=20) and rabbit plasma (n=3), and quantified the CETP activity by fluorimeter. Probucol served as positive control. Furthermore, we dosed CETP transgenic mice with leoligin and vehicle control by oral gavage for 7 days and measured subsequently the in vivo modulation of CETP activity (n=5 for each treatment group). RESULTS: In vitro, leoligin significantly activated CETP in human plasma at 100 pM (p=0.023) and 1 nM (p=0.042), respectively, whereas leoligin concentrations of 1 mM inhibited CETP activity (p=0.012). The observed CETP activation was not species specific, as it was similar in magnitude for rabbit CETP. In vivo, there was also a higher CETP activity after oral dosage of CETP transgenic mice with leoligin (p=0.015). There was no short-term toxicity apparent in mice treated with leoligin. CONCLUSION: CETP agonism by leoligin appears to be safe and effective, and may prove to be a useful modality to alter high-density lipoprotein metabolism.
Copyright é 2011 Elsevier Ireland Ltd. All rights reserved. - Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cholesterol Ester Transfer Proteins - agonists
- Humans -
- Lignans - administration and dosage
- Mice -
- Mice, Transgenic -
- Molecular Dynamics Simulation -
- Rabbits -
- Find related publications in this database (Keywords)
- Cholesterol metabolism
- High-density lipoproteins
- Cholesteryl ester transfer protein