Cholesterol-independent membrane disruption caused by triterpenoid saponins.

The membrane-disrupting activity of 15 triterpenoid saponins, obtained from Chinese plants of the genus Aralia, was investigated using phosphatidylcholine liposomes with and without cholesterol. The permeability of the membrane was examined by monitoring the induced fluorescent dye release from the liposome. On the basis of the obtained results, the structure-activity relationship among glucuronides of oleanolic acid was discussed. This takes into account particularly the variation in the carboxyl function. Namely, the saponins could induce a permeability change on liposomal membrane without cholesterol when they are glycosylated at both C-3 and C-28 of the oleanolic acid. There also exists a great similarity in the time-course curves for dye-release within such saponins, reflecting their similar action with the lipid bilayer membrane. The saponins glycosylated only at C-3 could also exhibit the same activity with somewhat different action profiles when the glucuronic acid is esterified, while those with the free glucuronic acid required cholesterol in the liposomes to induce permeability change thereof.