Saponins are plant secondary metabolites. There are associated with defensive roles due to their cytotoxicity and are active against microorganisms. Saponins are frequently targeted to develop efficient drugs. Plant biomass containing saponins deserves sustained interest to develop high-added value applications. A key issue when considering the use of saponins for human healthcare is their toxicity that must be modulated before envisaging any biomedical application. This can only go through understanding the saponin-membrane interactions. Quinoa is abundantly consumed worldwide, but the quinoa husk is discarded due to its astringent taste associated with its saponin content. Here, we focus on the saponins of the quinoa husk extract (QE). We qualitatively and quantitively characterized the QE saponins using mass spectrometry. They are bidesmosidic molecules, with two oligosaccharidic chains appended on the aglycone with two different linkages; a glycosidic bond and an ester function. The latter can be hydrolyzed to prepare monodesmosidic molecules. The microwave-assisted hydrolysis reaction was optimized to produce monodesmosidic saponins. The membranolytic activity of the saponins was assayed based on their hemolytic activity that was shown to be drastically increased upon hydrolysis. In silico investigations confirmed that the monodesmosidic saponins interact preferentially with a model phospholipid bilayer, explaining the measured increased hemolytic activity.

Sea cucumbers produce saponins as a chemical defense mechanism, however their cells can tolerate the cytotoxic nature of these chemicals. To elucidate the molecular mechanisms behind this tolerance a suite of complementary biophysical tools was used, firstly using liposomes for in vitro techniques then using in silico approaches for a molecular-level insight. The holothuroid saponin Frondoside A, caused significantly less permeabilization in liposomes containing a Δ7 holothuroid sterol than those containing cholesterol and resulted in endothermic interactions versus exothermic interactions with cholesterol containing liposomes. Lipid phases simulations revealed that Frondoside A has an agglomerating effect on cholesterol domains, however, induced small irregular Δ7 sterol clusters. Our results suggest that the structural peculiarities of holothuroid sterols provide sea cucumbers with a mechanism to mitigate the sterol-agglomerating effect of saponins, and therefore to protect their cells from the cytotoxicity of the saponins they produce.