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• W2117992023 abstract "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.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).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.CETP agonism by leoligin appears to be safe and effective, and may prove to be a useful modality to alter high-density lipoprotein metabolism." @default.
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• W2117992023 date "2011-11-01" @default.
• W2117992023 modified "2023-10-17" @default.
• W2117992023 title "Leoligin, the major lignan from Edelweiss, activates cholesteryl ester transfer protein" @default.
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• W2117992023 doi "https://doi.org/10.1016/j.atherosclerosis.2011.07.023" @default.
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