Mechanisms
Leoligin, a lignan from Edelweiss, is identified as a novel CETP activator (Atherosclerosis 2011)
Original title: Leoligin, the major lignan from Edelweiss, activates cholesteryl ester transfer protein
A pharmacophore-based screen suggested leoligin, the major lignan of Edelweiss (Leontopodium alpinum), might bind CETP, which was tested by incubating leoligin with human and rabbit plasma and by dosing CETP-transgenic mice orally for 7 days, using probucol as a positive control for CETP activation. In vitro, leoligin significantly activated CETP in human plasma at 100 pM (P equals 0.023) and 1 nM (P equals 0.042), an effect of similar magnitude in rabbit plasma, whereas 1 mM leoligin inhibited CETP activity (P equals 0.012). In vivo, oral leoligin also raised CETP activity in CETP-transgenic mice (P equals 0.015) with no apparent short-term toxicity, identifying leoligin as a safe, concentration-dependent modulator of CETP that can act as either agonist or inhibitor.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.