ABSTRACT
The in vitro interactions between triterpene glycoside, cucumarioside A(2)-2, isolated from the Far-Eastern holothurian Cucumaria japonica, and mouse splenocyte and peritoneal macrophage biomembranes were studied. Multiple experimental approaches were employed, including determination of biomembrane microviscosity, membrane potential and Ca(2+) signaling, and radioligand binding assays. Cucumarioside A(2)-2 exhibited strong cytotoxic effect in the micromolar range of concentrations and showed pronounced immunomodulatory activity in the nanomolar concentration range. It was established that the cucumarioside A(2)-2 effectively interacted with immune cells and increased the cellular biomembrane microviscosity. This interaction led to a dose-dependent reversible shift in cellular membrane potential and temporary biomembrane depolarization; and an increase in [Ca(2+)](i) in the cytoplasm. It is suggested that there are at least two binding sites for [(3)H]-cucumarioside A(2)-2 on cellular membranes corresponding to different biomembrane components: a low affinity site match to membrane cholesterol that is responsible for the cytotoxic properties, and a high affinity site corresponding to a hypothetical receptor that is responsible for immunostimulation.
Subject(s)
Cell Membrane/drug effects , Cucumaria/immunology , Glycosides/pharmacology , Saponins/pharmacology , Triterpenes/pharmacology , Animals , Calcium Signaling/drug effects , Cell Membrane/chemistry , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Female , Glycosides/chemistry , Glycosides/isolation & purification , Immunomodulation , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/ultrastructure , Membrane Potentials/drug effects , Mice , Mice, Inbred BALB C , Saponins/chemistry , Saponins/isolation & purification , Spleen/metabolism , Spleen/ultrastructure , Triterpenes/chemistry , Triterpenes/isolation & purification , Viscosity/drug effectsSubject(s)
Cucumaria/metabolism , Glycosides/pharmacokinetics , Triterpenes/pharmacokinetics , Tritium , Animals , Gastric Mucosa/metabolism , Glycosides/blood , Isotope Labeling/methods , Kidney/metabolism , Liver/metabolism , Mice , Mice, Inbred BALB C , Myocardium/metabolism , Spleen/metabolism , Triterpenes/bloodABSTRACT
Two new steroid glycosides: distolasteroside D6, (24S)-24-O-(beta-D-xylopyranosyl)-5alpha-cholestane-3beta,6alpha,8,15beta,16beta,24-hexaol, and distolasteroside D7. (22E,24R)-24-O-(beta-D-xylopyranosyl)-5alpha-cholest-22-ene-3beta,6alpha,8,15beta,24-pentaol were isolated along with the previously known distolasterosides D1, D2, and D3, echinasteroside C, and (25S)-5alpha-cholestane-3beta,4beta,6alpha,7alpha,8,15alpha,16beta,26-octaol from the Far Eastern starfish Distolasterias nipon. The structures of new compounds were elucidated by NMR spectroscopy and MALDI TOF mass spectrometry. Like neurotrophins, distolasterosides D1, D2, and D3 were shown to induce neuroblast differentiation in a mouse neuroblastoma C 1300 cell culture.
Subject(s)
Glycosides/isolation & purification , Starfish/chemistry , Steroids/isolation & purification , Animals , Cell Differentiation/drug effects , Cell Line, Tumor , Glycosides/chemistry , Glycosides/pharmacology , Mice , Neuroblastoma/metabolism , Neuroblastoma/pathology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Steroids/chemistry , Steroids/pharmacologyABSTRACT
Sapogenins from the starfish Asterias amurensis and Lethasterias nanimensis chelifera, 5 alpha-pregn-9(11)-ene-3 beta,6 alpha-diol-20-one, 5 alpha-cholest-9(11)-ene-3 beta,6 alpha-diol-23-one, 5 alpha-cholesta-9(11),24(25)-diene-3 beta,6 alpha-diol-23-one, (20E)-5 alpha-cholesta-9(11),20(22)-diene-3 beta,6 alpha-diol-23-one and 24 zeta-methyl-5 alpha-cholesta-9(11),20(22)-diene-3 beta,6 alpha-diol-23-one, stimulated the contractile force of the heart of the mollusk Spisula sachalinensis at concentration of 5 x 10(-5) M. Ouabain, a specific inhibitor of Na+,K(+)-ATPase, at concentration of 5 x 10(-5) M had no effect on this physiological model. Starfish sapogenins of the cholestane series moderately inhibited rat brain cortex Na+,K(+)-ATPase and decreased Ca2+ influx into Ehrlich carcinoma cells. In contrast, pregnane asterogenin asterone did not inhibit Na+,K(+)-ATPase and increased the influx of Ca2+ into cells. These effects were not the result of cell membrane damage, because none of the compounds tested have hemolytic activity.
Subject(s)
Calcium/metabolism , Heart/drug effects , Sapogenins/pharmacology , Saponins/pharmacology , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Animals , Brain/drug effects , Brain/enzymology , Cell Membrane/drug effects , Cell Membrane/metabolism , Cholestenones/pharmacology , Enzyme Inhibitors/pharmacology , Hemolysis/drug effects , Humans , Mollusca , Myocardial Contraction/drug effects , Ouabain/pharmacology , Pregnenes/pharmacology , Rats , Sapogenins/chemistry , Sapogenins/isolation & purification , Starfish , Sterols/pharmacology , Tumor Cells, CulturedABSTRACT
The saponins, conjugated sterols, and free sterols of the sea cucumber Eupentacta fraudatrix were examined. A total of 85 steroids, twelve of them new, were identified in the free sterol, sulfated sterol, and sterol-xyloside fractions. The free sterol fraction contained 4 alpha,14 alpha-dimethylcholest-9(11)-en-3 beta-ol(6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol(7) together with 18 minor sterols. Examination of the aglycone moieties of the sterol-beta-xyloside fraction afforded 31 different sterols. Cholestan-3 beta-ol (15) and 24-methylcholesta-7,22-dien-3 beta-ol (20) were the major sterols in this group. Cholestanol sulfate (74) and cholesterol sulfate (64) were identified as the major components among the 34 different sterol sulfates present. Finally, cucumariosides G1 (1), C1 (2), C2 (3), H (4), and G2 (5) were isolated from the saponin fraction. Radiolabeling experiments indicated that there are two pathways of sterol biosynthesis in E. fraudratix. The first involves transformation of squalene to produce lanosta-9(11),24-dien-3 beta-ol(parkeol) which is subsequently demethylated to form 4 alpha,14 alpha-dimethylcholest-9(11)-en-3 beta-ol (6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol (7). The second proceeds through squalene to lanosterol which is further metabolized to produce the triterpene saponins, 5 alpha-cholest-7-en-3 beta-ol (19) and its xyloside (49).
Subject(s)
Sea Cucumbers/metabolism , Steroids/biosynthesis , Triterpenes/metabolism , Animals , Cholestanol/analogs & derivatives , Cholesterol/analogs & derivatives , Molecular Structure , Saponins/biosynthesis , Saponins/chemistry , Steroids/chemistry , Sterols/biosynthesis , Sterols/chemistry , Sulfates/metabolismABSTRACT
A series of 23-oxosteroid derivatives have been synthesized and tested for their inhibiting Na+, K(+)-dependent ATPase from rat brain in the 1 x 10(-6)-1 x 10(-4) M concentrations. Natural 23-oxogenins from sea star Asterias amurensis and synthetic monoesters showed the inhibiting activity upto 50-55%. These compounds caused heart contraction in frogs at the level of the known cardiotonic strophanthin G, and inotropic activity on isolated heart of mollusk Spisula sachalinensis.
Subject(s)
Cardiac Glycosides/pharmacology , Myocardial Contraction/drug effects , Animals , Anura , Brain/drug effects , Cardiac Glycosides/chemical synthesis , In Vitro Techniques , Mollusca , Rats , Sea Anemones , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitorsABSTRACT
1. The cytostatic and antimicrobial activity of triterpene glycosides of 19 holothurian species of the Pacific tropical zone has been studied. 2. It has been demonstrated that yeast and tumor cells display a comparable sensibility to the action of triterpene oligosides of sea cucumbers. 3. Gram-positive and Gram-negative bacteria are not sensible to the action of glycosides in doses to 500 mkg/ml. 4. Triterpene glycosides-stichoposides, thelothurins and oligosides of Holothuria of genus Bohadschia are the most active in relation to fungal, yeast microflora and tumor cells.
