1. Sci Rep. 2019 May 13;9(1):7285. doi: 10.1038/s41598-019-43674-w.

The activity of the saponin ginsenoside Rh2 is enhanced by the interaction with
membrane sphingomyelin but depressed by cholesterol.

Verstraeten SL(1)(2), Deleu M(3), Janikowska-Sagan M(4), Claereboudt EJS(3), Lins
L(3), Tyteca D(2), Mingeot-Leclercq MP(5).

Author information: 
(1)Université catholique de Louvain, Louvain Drug Research Institute, Cellular & 
Molecular Pharmacology Unit, 1200, Brussels, Belgium.
(2)Université catholique de Louvain, de Duve Institute, Cell Biology Unit, 1200, 
Brussels, Belgium.
(3)Université de Liège (ULiège), Gembloux-Agro-Bio Tech, Molecular Biophysics at 
Interfaces Unit, 5030, Gembloux, Belgium.
(4)Jagiellonian University, Faculty of Physics, Astronomy and Applied Computer
Science, 30-348, Krakow, Poland.
(5)Université catholique de Louvain, Louvain Drug Research Institute, Cellular & 
Molecular Pharmacology Unit, 1200, Brussels, Belgium.
marie-paule.mingeot@uclouvain.be.

The membrane activity of some saponins, such as digitonin or alpha-hederin, is
usually attributed to their interaction with membrane cholesterol (Chol). This
contrasts with our recent publication showing that Chol, contrary to
sphingomyelin (SM), can delay the cytotoxicity of the saponin ginsenoside Rh2,
challenging the usual view that most saponins mediate their membrane effects
through interaction with Chol. The aim of the present study was to elucidate the 
respective importance of Chol and SM as compared to phosphatidylcholine (PC)
species in the membrane-related effects of Rh2. On simple lipid monolayers, Rh2
interacted more favorably with eggSM and DOPC than with Chol and eggPC. Using
Large Unilamellar Vesicles (LUVs) of binary or ternary lipid compositions, we
showed that Rh2 increased vesicle size, decreased membrane fluidity and induced
membrane permeability with the following preference:
eggSM:eggPC > eggSM:eggPC:Chol > eggPC:Chol. On Giant Unilamellar Vesicles
(GUVs), we evidenced that Rh2 generated positive curvatures in eggSM-containing
GUVs and small buds followed by intra-luminal vesicles in eggSM-free GUVs.
Altogether, our data indicate that eggSM promotes and accelerates
membrane-related effects induced by Rh2 whereas Chol slows down and depresses
these effects. This study reconsiders the theory that Chol is the only
responsible for the activity of saponins.

DOI: 10.1038/s41598-019-43674-w 
PMCID: PMC6513819
PMID: 31086211