Investigations of the Mechanism of Membrane Activity of Selected Triterpenoid Saponins

Abstract

The experiments with different triterpenoid saponins showed a significant difference in the microphysiometric activity between acylated and non-acylated compounds. Only acylated saponins in low concentrations were able to activate the metabolism of endothelial cells after short-time incubation in a transient manner lasting approximately 2 hours. The strongest effect was produced by virgaureasaponin b, an incubation with 4 μg/ml over 6 min induced a stimulation of the metabolic activity of 190 % maximum after 30 min. This treatment did not induce non-reversible toxic effects, and could be repeated in the same way after a recovery period. The saponins without acylation in the glycosidic part did not induce metabolic stimulation, even in concentrations higher than observed for the acylated compounds. The current interpretation of the results is connected with the suggestion that especially acylated saponins are able to integrate into the cellular membrane transiently. This integration might induce pore-like structures which change the membrane permeability associated with alterations in the ionic homeostasis between intracellular and extracellular compartments.

Key words

Saponins - membrane - cytotoxicity - microphysiometry - mechanism of action

References

• 1 Foulkes E C. Toxic effects on membrane structure and function. In: Foulkes, EC Biological Membranes in Toxicology. Taylor & Francis 1998: 59-88
• 2 Parce J W, Owicki J C, Kercso K M, Signal G B, Wada H G, Muir V C, et al. Detection of cell-affecting agents with a silicon biosensor.  Science. 1989;  246 243-7
• 3 Vestweber D. Molecular mechanisms that control endothelial cell contacts.  Journal of Pathology. 2000;  190 281-91
• 4 Prausnitz M R, Noonan J S. Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye.  Journal of Pharmaceutical Sciences. 1988;  87 1479-88
• 5 Bader G, Wray V, Hiller K. The main saponins from the aerial parts and the roots of Solidago virgaurea subsp. virgaurea .  Planta Medica. 1995;  61 158-61
• 6 Siepmann C, Bader G, Hiller K, Wray V, Domke T, Nimtz M. New saponins from the seed of Agrostemma githago var. githago .  Planta Medica. 1998;  64 159-64
• 7 Melzig M F, Loose R. Inhibition of lipopolysaccharide (LPS)-induced endothelial cytotoxicity by diosmin.  Pharmazie. 1999;  54 298-9
• 8 Dathe M, Kaduk C, Tachikawa E, Melzig M F, Wenschuh H, Bienert M. Proline at position 14 of alamethicin is essential for hemolytic activity, catecholamine secretion from chromaffine cells and enhanced metabolic activity in endothelial cells.  Biochimica et Biophysica Acta. 1998;  1370 175-83
• 9 McConnell H M, Owick J C, Parce J W, Muir V C. The Cytosensor® Microphysiometer: Biological applications of silicon technology.  Science. 1992;  257 1906-12
• 10 Altomare C, Carotti A, Trapani G, Liso G. Estimation of partitioning parameters of nonionic surfactants using calculated descriptors of molecular size, polarity, and hydrogen bonding.  Journal of Pharmaceutical Sciences. 1997;  86 1417-25
• 11 Owicki J C, Parce J W. Biosensors based on the energy metabolism of living cells: The physical chemistry and cell biology of extracellular acidification.  Biosensors and Biolelectronics. 1992;  7 255-72
• 12 Barbato F, La Rotonda M L, Quaglia F. Chromatographic indexes on immobilized artificial membranes for local anesthetics: Relationship with activity data on closed sodium channels.  Pharmaceutical Research. 1997;  14 1699-705
• 13 Bader G. Pharmakologische und biopharmazeutische Bewertung von Triterpensaponinen.  Pharmazie. 1994;  49 391-400
• 14 Tschesche R, Wulff G. Chemie und Biologie der Saponine. In: Herz W, Grisebach H, Kirby GW, editors Fortschritte der Chemie organischer Naturstoffe Vol. 30. Wien, New York; Springer 1973: 461-606
• 15 Plohmann B, Bader G, Hiller K, Franz G. Immunomodulatory and antitumoral effects of triterpenoid saponins.  Pharmazie. 1997;  52 953-7