Mechanistic Investigation of Interactions between Steroidal Saponin Digitonin and Cell Membrane Models

Abstract

Digitonin is an amphiphilic steroidal saponin, a class of natural products that can bind to cholesterol and lyse cells. Despite the known cell membrane lysis activity, it remains unclear how it interacts with cell membranes. In the present work, the interaction mechanism between digitonin and cell membrane models has quantitatively been investigated using a combination of physical techniques. It has been demonstrated that digitonin molecules bind specifically to cholesterol in the membrane, resulting in the formation of cholesterol-digitonin complexes on the membrane surface by removing cholesterol from the membrane core. Changes in the mass density and the film mechanics caused by the digitonin were determined by using quartz crystal microbalance with dissipation (QCM-D), and the combination of X-ray reflectivity (XRR) and dual polarization interferometry (DPI) yielded the hydration level of the cholesterol-digitonin complexes. From differential scanning calorimetry (DSC) analysis, supporting evidence was obtained that cholesterol was removed from the membrane core.

Modes of Action of Herbal Medicines and Plant Secondary Metabolites

“…Lipophilic SM can also modulate the activity of ion channels; a well-known example is that of mint oil which affects calcium channels and the motility of smooth muscles cells in the intestines [11,12,13]. A special class of membrane active SM exist in saponins (see below) which can complex cholesterol in animal membranes and ergosterol in fungal membranes [11,12,13,23,24,85]. As a consequence of interactions of monodesmodisic saponins (with a single sugar chain) with cells, membranes are completely lysed.…”

“…As described above (Figure 3), monodesmosidic saponins are amphiphilic compounds, which can complex cholesterol in biomembranes with their lipophilic terpenoid moiety and bind to surface glycoproteins and glycolipids with their sugar side chain [23,77,85]. This leads to a severe tension of the biomembrane and leakage.…”

In vitro and ex vivo strategies for intracellular delivery

“…The amphiphilic plant glycosides digitonin and saponins are the most popular detergents for reversible permeabilization of cells 47,48 . Although the exact mechanisms are still a matter of study 69 , it is known that digitonin and saponin interact with membrane cholesterol, making them specific for the cholesterol-rich plasma membrane.…”

Protection of the biconcave profile of human erythrocytes against osmotic damage by ultraviolet-A irradiation through membrane-cytoskeleton enhancement

“…Saponin, the steroid or triterpenoid glycosides, can interact with the cell membrane because of the affinity of the aglycone moiety for membrane cholesterol, 22,23 which induces vesiculation and pore formation in cell membranes, even resulting in disruption of the membrane-skeleton system at high concentration. We used saponin (S4521, Sigma-Aldrich, St Louis, MO, USA) to further investigate whether the UVA-induced protective effect on erythrocytes shape is associated with the membrane-skeleton system.…”