Abstract
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.
Highlights
Cholesterol (Chol) and sphingomyelin (SM) are essential components of mammalian plasma membranes, constituting around 35 and 25% of total lipids present in the outer plasma membrane leaflet, respectively[1]
We first evaluated the interaction of Rh2 with membrane in silico and Langmuir experiments on simple lipid monolayers composed of egg sphingomyelin, egg phosphatidylcholine, www.nature.com/scientificreports
We evaluated the consequences of Rh2 membrane adsorption on liposome size and a set of biophysical parameters determined on Large Unilamellar Vesicles (LUVs) or Giant Unilamellar Vesicles (GUVs) containing egg sphingomyelin (eSM) or Chol or both of them
Summary
Cholesterol (Chol) and sphingomyelin (SM) are essential components of mammalian plasma membranes, constituting around 35 and 25% of total lipids present in the outer plasma membrane leaflet, respectively[1]. Studies over the last decades have suggested for the presence of transient nanometric domains enriched in Chol and SM, forming a liquid-ordered (Lo) phase[3,4,5] These highly ordered membrane domains have been proposed to serve as platforms for signaling pathways involved in cell adhesion and migration as well as cell survival and proliferation with potential implications in cancer development[6]. Saponins, amphiphilic compounds widely found in plants, are attracting more and more attention based on their numerous biological activities including anticancer properties Many of these effects seem to be related to their ability to interact and modify the plasma membrane properties, such as fluidity or permeability[7]. To the best of our knowledge, this study is the first to reveal the protective role of Chol in membrane-related effects induced by Rh2
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
