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Rund 60 Millionen Menschen aus 37 Ländern Afrikas stehen unter dem ständigen Risiko der unbehandelt tödlich verlaufenden Schlafkrankheit. Die Viehseuche Nagana ist der Hauptgrund, warum neun Millionen Quadratkilometer, das heißt etwa die Hälfte des kultivierbaren Landes in Afrika nicht für intensive Viehzucht genutzt werden kann. Die Krankheit wird bei Mensch und Tier durch mehrere Trypanosomenarten hervorgerufen, die hauptsächlich mit konventionellen Arzneistoffen behandelt werden, in manchen Fällen auch mit traditionell verwendeten Heilpflanzen. Da es zahlreiche Probleme mit der derzeit verfügbaren Therapie mit konventionellen Arzneistoffen gibt, war Ziel dieser Arbeit, die Wirkung einiger dieser Heilpflanzen besser beurteilen zu können und deren Anwendbarkeit nach Möglichkeit zu optimieren. Dabei wurden 47 Dichlormethanextrakte von Pflanzenteilen aus 37 Heilpflanzenarten im in vitro Modell an dem Erreger Trypanosoma brucei brucei auf ihre trypanozide Aktivität untersucht. 13 Extrakte zeigten Aktivität mit MHK-Werten von ≤ 100 µg/ml. Sechs Extrakte wiesen MHK-Werte von 50 µg/ml auf und wurden in einem in vivo Test an Mäusen weiter untersucht. Dabei konnten der Blattextrakt von Guiera senegalensis und der Wurzelextrakt von Securidaca longepedunculata die Parasitämie zuvor mit T. b. brucei infizierter Mäuse um 41 beziehungsweise 49 % reduzieren. Die anschließende phytochemische Untersuchung der Wurzel von S. longepedunculata zeigte, dass für die festgestellte therapeutische Wirkung die reichlich vorkommenden Saponine eine interessante Rolle spielen. Die Wirksamkeit von Saponinen gegen Trypanosomen wurde in den letzten 40 Jahren nicht dokumentiert. Ein erster Vergleich mit bereits bekannten Saponinen zeigt, dass eine gewisse Selektivität der in dieser Arbeit isolierten Saponinfraktion gegeben ist. Als Nebenprodukt aus der aktivitätsgeleiteten Fraktionierung konnte aus der Wurzel von S. longepedunculata ein Saccharose- Derivat isoliert werden, das bisher nur in der Stammrinde gefunden wurde. Während des in vivo Versuchs konnte als interessanter Nebeneffekt ein Anstieg der Parasitämie auf das 2,7-fache nach Behandlung mit dem Extrakt der Stammrinde von Acacia nilotica festgestellt werden. Dies deutet auf einen bisher unbekannten immunsuppressiven Effekt des Extraktes hin., Approximately 60 million people from 37 sub-Saharan African countries are at risk of contracting sleeping sickness, a fatal disease if left untreated. The epizootic disease nagana in livestock is the main reason why nine million square kilometres, about half of the cultivable land in Africa cannot be used for intensive livestock farming. The disease in humans and animals is caused by various trypanosome species that are mainly controlled by chemotherapy using conventional drugs and in some instances medicinal plants. Due to the numerous problems associated with the conventional drug therapy, the aim of this work was to evaluate the effect of some of these medicinal plants and to optimize their utilization. Trypanocidal activity of 47 dichloromethane extracts from plant parts of 37 medicinal plant species was investigated in an in vitro model using Trypanosoma brucei brucei. 13 extracts showed activity with MHC-values of ≤ 100 µg/ml. Six extracts showed MHC-values of 50 µg/ml and were further examined in an in vivo test with mice. The leaf extract from Guiera senegalensis and the root extract from Securidaca longepedunculata reduced the parasitaemia of T. b. brucei infected mice by 41 and 49 % respectively. Subsequent phytochemical investigation of S. longepedunculata roots indicated that the richly occurring saponins play an interesting role for the noted therapeutic efficacy. The activity of saponins against trypanosomes has not been documented over the last 40 years. A first comparison with well-known saponins showed a certain selectivity of the saponin fraction, isolated in this work. As a by-product of activity guided fractionation a sucrose derivative could be isolated from S. longepedunculata roots that has only been found in the stem bark before. During the in vivo test, a 2,7-fold increase in parasitaemia was detected as an interesting side effect post-treatment with Acacia nilotica stem bark extract. All indications show that the extract has an unknown immunosuppressive effect.

Triterpenoide Saponine aus Gypsophila paniculata L. sind dafür bekannt, die Zytotoxizität spezieller Toxine drastisch zu steigern. Bei diesen Toxinen handelt es sich um Ribosomen-inaktivierende Proteine Typ I (RIPs Typ I), die durch ihre N-Glycosidase-Aktivität einen essentiellen Adeninrest von der ribosomalen RNA abspalten, so dass die Proteinsynthese zum Erliegen kommt. Bisherige Untersuchungen führten die Saponin abhängige außerordentliche Zytotoxizitätssteigerung Ribosomen-inaktivierender Proteine Typ I auf eine Saponin induzierte Modulation der Endozytose oder Phagozytose zurück. Ausgehend von dieser Arbeitshypothese wurden nach Etablierung geeigneter In- vitro-Modelle die Endozytose, Exozytose und Phagozytose modulierenden Eigenschaften der Gypsophilasaponine untersucht. Durch Gypsophilasaponine konnte jedoch weder die Phagozytose nichtopsonierter oder opsonierter Escherichia-coli-Bakterien noch die Aufnahme von Latex-Partikeln induziert werden. Die weiteren, im Rahmen dieser Arbeit durchgeführten Untersuchungen hatten die Charakterisierung der synergistischen Zytotoxizität zum Ziel. In ECV-304-Zellen wurde die GI50 des Saporins (RIP Typ I), in Kombination mit Gypsophilasaponinen mit 42×10−12 M bestimmt und war mit der GI50 (21×10−12 M) des hoch toxischen Ribosomen-inaktivierenden Proteins Typ II, Viscumin, vergleichbar. Diese außerordentliche Toxizitätssteigerung des Saporins war nicht auf ECV-304-Zellen beschränkt und konnte in weiteren sechs humanen Zelllinien beobachtet werden. Dies deutet auf einen allgemeinen Saponin abhängigen Mechanismus der Zytotoxizitätssteigerung Ribosomen-inaktivierender Proteine Typ I hin. Die Beobachtung, dass Inhibitoren der Clathrin vermittelten Endozytose zu einer Hemmung der Saponin/Saporin-Zytotoxizität führten, unterstreicht zudem die Bedeutung der Clathrin vermittelten Endozytose bei der Saporininternalisierung. Gypsophilasaponine übten jedoch weder einen stimulatorischen Einfluss auf die Clathrin vermittelte Endozytose noch auf die Exozytose internalisierten Saporins aus. Ein modulatorischer Einfluss der Gypsophilasaponine auf den Saporinabbau konnte ebenfalls ausgeschlossen werden. Weitere im Rahmen dieser Arbeit durchgeführte Untersuchungen deuten auf eine Saponin induzierte, endosomale Freisetzung der mittels Clathrin vermittelter Endozytose internalisierten RIPs Typ I hin. Dieser, im Angloamerikanischen als endosomal escape bezeichnete, durch Gypsophilasaponine katalysierte Saporintransfer liegt der außerordentlichen Saporin-Toxizitätssteigerung als Mechanismus zu Grunde. Da die Endosomenmembran nicht vollständig lysiert wird und nur sehr wenige Toxinmoleküle das Zytosol zu erreichen scheinen, kommt der enzymatischen Aktivität des Saporins mit 140 pmol Adenin/pmol Saporin pro Stunde eine besondere Rolle zu. Dadurch kann die geringe, Saponin vermittelte Saporintransfereffizienz auf zytosolischer Seite kompensiert werden. In Analogie zu den Ionophoren können Gypsophilasaponine demgemäß als Enzymophore aufgefasst werden., Triterpenoid saponins from Gypsophila paniculata L. are known to enhance the cytotoxicity of type I ribosome-inactivating proteins (type I RIP). These proteins exhibit N-glycosidase activity and remove an essential adenine residue from the ribosomal RNA. Up to now it was assumed that the saponin- mediated toxicity enhancement of these toxins is due to a an increased endocytosis or phagocytosis in saponin treated cells. To scruntinize this hypothesis, appropriate in vitro models were established and the influence of Gypsophila saponins on endocytosis, exocytosis and on phagocytosis was investigated. Gypsophila saponins showed no influence on the phagocytosis of opsonated and non-opsonated Escherichia coli-bacteria. This was also observed for microspheres. In combination with Gypsophila saponins the cytotoxicity of saporin (type I RIP) was increased to a level similar to that of the highly toxic type II RIP rViscumin. rViscumin achieved an IC50 value of 21.5×10−12 M on ECV-304 cells and the combination of saporin with Gypsophila saponins 42.5×10−12 M. This tremendous toxicitiy enhancement was not restricted to ECV-304 cells but was observed in six further cell lines, indicating a general saponin dependent mechanism of toxicity enhancement of type I ribosome- inactivating proteins. It was further shown, that the internalization of saporin was mediated by clathrin-mediated endocytsosis. However Gypsophila saponins did not modulate the clathrin- mediated endocytosis of saporin. This was also shown for other transport processes such as exocytosis. Degradation processes of saporin were also not influenced by the saponins. Further experiments showed a saponin-mediated endosomal escape of the N-glycosidase saporin. Additional investigations indicate that only few saporin molecules traverse through the endosomal membrane into the cytosol of saponin-treated cells. These low saporin penetration rate through endosomal membranes could be balanced by the strong N-glycosidase activity of saporin with up to 140 pmol adenine/pmol saporin per h. In this context and in analogy to ionophores Gypsophila saponins could be defined as enzymophores.

Saponins are glycosides found in many plants, which have soap character due to their surfactant properties. They work haemolytic and may cause symptoms of intoxication in high concentration. Among therapeutically relevant effects expectorative, anti-inflammatory and immune-stimulating effects have the highest ranking. Beyond that, saponins demonstrate antimicrobial properties particularly against fungi and additionally against bacteria and protozoa. In animal nutrition additions of saponins can suppress intestinal and ruminal ammonia production. The ammonia-reducing effect is primarily attributed to an inhibition of proteolytic microorganisms. Due to reduced NH3-concentrations metabolism is relieved, which offers benefits to animal welfare and animal performance. Accordingly improved feed convertion ratio can be registered in weanling and growing-finishing pigs with the employment of saponin-containing feed additives. With regard to ruminal fermentation in vitro and in vivo studies have shown that beside proteolytic protozoa also cellolytic and amylolytic bacterial species are restrained. To what extent antimicrobial activity supress digestion or whether the selective effects on microorganisms can be used purposefully to manipulate ruminal fermentation, must be clarified in further investigations.

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An insufficient neutralization of chlorhexidine (4%), tested in vitro against Enterococcus faecium ATCC 6057, was suspected in the quantitative suspension test although the combination Tween 80, cysteine, histidine and saponine was assessed as sufficient for neutralising chlorhexidine. Bactericidal activity of each neutralising compound and their combinations was excluded. Sufficient neutralization was observed when all dilution steps and the corresponding agar plates were supplemented with the neutralising compounds. Successful neutralization in broth is not equivalent with successful neutralization in tryptic saline. We suggest to supplement at least the agar plates of the first dilution step with neutralising compounds when testing chlorhexidine.

Endogenous digitalis-like factor (EDLF), an inhibitor of membrane Na+/K(+)-ATPase, is discussed to be involved in the pathogenesis of cirrhogenic portal hypertension, ascites formation and development of functional hepatorenal failure. Therefore, we investigated the serum content of this mediator in patients with liver cirrhosis Child-Pugh stage A, B, and C (n = 27) by means of enzyme immunoassay with a specific digoxin antibody. Furthermore, a correlation analysis was performed in order to find out correlations between signs of cell injury, cholestasis, synthetic cell function, ascites formation, and hepatorenal failure. Our results demonstrate that EDLF is significantly elevated in Child C cirrhosis (0.61 +/- 0.15 ng/ml) in comparison to Child A cirrhosis (0.013 +/- 0.2 ng/ml) and is also higher than in Child B cirrhosis (0.23 +/- 0.25 ng/ml). In patients without ascites EDLF (0.056 +/- 0.19 ng/ml) differs significantly from that of patients with non-complicated ascites (0.156 +/- 0.176 ng/ml) and from that of patients with therapy refractory ascites (0.66 +/- 0.17 ng/ml) or hepatorenal failure (1.56 ng/ml). There are no correlations between EDLF and renal function. Significant correlations were demonstrated for cholestasis (serum bilirubin), synthesis function (serum protein, Quick's value, cholinesterase, fibrinogen, albumin), and the degree of portasystemic encephalopathy (number connection test). We conclude that EDLF may act as a mediator in the process of progressive portal hypertension and its complications due to cirrhosis. This process of progression is caused by the inhibition of Na+/K(+)-ATPase, vasoconstriction, and endothelin secretion.

Four new main saponins (canadensis-saponins 5-8) (compounds 5-8) were isolated from Solidago canadensis L. (Asteraceae). Using GC/MS, FAB-MS, and mainly 2D-NMR techniques their structures were identified as 3-O-[beta-D-glucopyranosyl(1----3)-beta-D- glucopyranosyl]-28-O-[beta-D-galactopyranosyl(1----2)-alpha-L- rhamnopyranosyl-(1----3)-beta-D-xylopyranosyl-(1----4)-[beta-D- xylopyranosyl-(1----3)]-alpha-L-rhamnopyranosyl-(1----2)-[beta-D-apio -D- furanosyl-(1----3)]-beta-D-6-deoxyglucopyranosyl-(1----)]-bayog enin(5),3-O- [beta-D-glucopyranosyl-(1----3)-beta-D-glucopyranosyl]-28-O-[beta-D- galactopyranosyl-(1----2)-alpha-L-rhamnopyranosyl-(1----3)-beta-D- xylopyranosyl-(1----4)-[beta-D-xylopyranosyl-(1----3)]-alpha-L- rhamnopyranosyl-(1----2)-[beta-D-apio-D-furanosyl-(1----3)]- arabinopyranosyl-(1----)]bayogenin(6),3-O-[beta-D-glucopy ran osyl-(1----3)- beta-D-glucopyranosyl]-28-O-[beta-D-galactopyranosyl-(1----2)- alpha-L-rhamnopyranosyl-(1----3)-beta-D-xylopyranosyl-(1----4)-[beta-D- xylopyranosyl-(1----3)]-alpha-L-rhamnopyranosyl-(1----2)-[alpha-L- rhamnopyranosyl-(1----3)]-beta-D-6-deoxyglucopyranosyl-(1----)]-++ +bayogenin (7), and 3-O-[beta-D-glucopyranosyl-(1----3)-beta-D-glucopyranosyl]-28-[O- beta-D-galactopyranosyl-(1----2)-alpha-L-rhamnopyranosyl-(1----3)-beta-D - xylopyranosyl-(1----4)-[beta-D-xylopyranosyl-(1----3)]-alpha-L- rhamnopyranosyl-(1----2)-[alpha-L-rhamnopyranosyl-(1----3)]arabinopyr anosyl - (1----)[-bayogenin (8).

Three new bisdesmosidic triterpenoid saponins, helianthoside 1(1), 2(2), and 3(3), were isolated from the flowers of Helianthus annuus L. and a new monodesmoside 4 was isolated after the cleavage of the ester-glycosidic linkages of 2 and 3. The structures of the compounds were elucidated by 13C-NMR, FAB-MS, GC/EI-MS of partially methylated alditol acetates and degradation methods.

From the chinese drug "Daxueteng" (Caulis Sargentodoxae: Sargentodoxa cuneata (Oliv.) Rehd. et Wils.; syn. Holboellia cuneata Oliv.) (Sargentodoxaceae), catechin and two known triterpene saponins, rosamultin (7) and kajiichigoside F1 (8) have been isolated. Some hitherto unknown reaction products of the saponins are described. Both 7 and 8 show haemolytic and in vitro antiviral activity.

The existence of an endogenous natriuretic hormone and ouabain-like factors (OLF) has been postulated for many years. This postulate was based on our original observation that a small M.W. fraction in the serum after acute expansion of the extracellular fluid volume (ECFV) not only exhibited natriuretic activity but also inhibited the Na-K-ATPase enzyme in vitro similar to ouabain. Since then, numerous studies confirmed the presence of OLFs in serum, urine, cerebrospinal fluid, and various organs including the heart and hypothalamus. Some of these OLFs are well-known endogenous compounds, such as free unsaturated fatty acids, which inhibit in vitro transmembranous sodium transport, Na-K-ATPase and 3H-ouabain binding to its membrane receptor or cross-react with digoxin antibodies. Chemically yet undefined OLFs of potentially hypothalamic origin were detected in various models of experimental and clinical hypertension and are suggested to play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs isolated from the urine of salt-loaded healthy subjects strongly enhance basal and vasopressin-stimulated release of calcium in vascular smooth muscle cells and platelets similar to the effects we had observed with endothelin. This urine fraction also exhibits natriuretic activity which increases in parallel with sodium intake. Further chromatographic separation and amino acid analysis confirmed the peptidic nature (M.W. less than 1000) of the natriuretic factor(s). However, the two biological activities, namely natriuretic and ouabain-like activities, reside in distinct and chemically different compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

A saponin fraction has been isolated from the ethanolic extract of Grindeliae herba. The saponin fraction showed strong haemolytic activity. The saponins were detected after separation on TLC by their color reactions and Rf values as well as by their haemolytic activity on blood agar. After hydrolysis, the chemical reactions and Rf values of the sapogenins were described. The main sapogenin was isolated by preparative chromatography and its structure was elucidated by mass, 1H-NMR, 13C-NMR, IR, and UV spectra. The compound is a new natural triterpenoid sapogenin lactone and is named grindeliasapogenin D. Spectral evidence is presented to establish its structure as 2 beta,3 beta,16 alpha,23-tetrahydroxyoleanan-28,13 beta-olide. Two further sapogenins present in small amounts were identified chromatographically as oleanolic acid and bayogenin using authentic reference substances. The aerial parts of Grindelia robusta Nutt, and G. lanceolata Nutt. (Asteraceae) (as well as two commercial extracts) were also investigated with respect to their saponin fraction. The 3 sapogenins mentioned above were detected in all samples. The antibiotic potency of the crude drug is not associated with the saponin fraction but is at least partially due to the resin fraction.

Triterpenoid glycosides obtained from Solidago virgaurea L. and Bellis perennis L. (Asteraceae) inhibit the growth of human-pathogenic yeasts (Candida and Cryptococcus species). First results are given of the investigations on the mode of action and the relationships between structure and activity of these compounds. The intensity of growth inhibition is influenced particularly by the carbohydrate chains of the glycosides. Monodesmosidic as well as bisdesmosidic glycosides of polygalacic acid exert fungicidic effects.

The estimation of serum digoxin is a usual method in intensive care. In a case report the detection of digoxin-like-immunoreactive-factor (DLIF) is shown, which gives false high levels. DLIF is observed in renal damage, high cardiac activity, pregnancy and newborn.

A digoxin-like immunoreactivity (DLIS) was measured by two routinely used clinical digoxin-immunoassays (radio- and enzymeimmunoassay) in cord blood of 255 newborns, in sera of their mothers at birth and in sera of 211 newborns during the first two postpartal weeks. The highest DLIS levels were found in serum of neonates at the first day of life (median: 0.23 ng/ml, 25% and 75% percentile: 0.19 and 0.28 ng/ml) and in cord blood (median: 0.21 ng/ml, 25% and 75% percentile: 0.19 and 0.24 ng/ml); maternal serum was shown to have three times less DLIS (median: 0.08 ng/ml, 25% and 75% percentile: 0.05 and 0.10 ng/ml). There was no significant correlation between DLIS concentrations in serum of newborns, cord blood or pregnants. The DLIS serum levels of preterms with birthweight less than 2500 g and gestational age less than 37 weeks were significantly lower than those of normal neonates at term (p less than 0.01); concomitantly the lowest DLIS levels were found in maternal serum of preterms (p less than 0.01). These observations strongly suggest rather a DLIS origin in the newborn than in the mother. During the first two postpartal weeks the DLIS concentration of a vast majority of the 211 newborns (91%) decreased continuously to one half of the starting value. Within the second postpartal week preterms were found to have a significantly delayed decrease in the DLIS serum levels (p less than 0.01). Small for date newborns showed no difference in their postpartal DLIS time course compared to normal neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

In the renal compensatory adaptation after the definition and the description of the fundamental phenomena of the functional compensation as well as of the structural adaptation is reported on mediator concepts and on modulations of the renal adaptation processes. Issuing from the central position of the sodium balance a mediator concept on natriuretic hormones (Auriculin and Endoxin) is developed which is supplemented by the renotropin mediator concept. The authors deal with the modulation of the renal compensatory adaptation (e.g. influences of age diet and so on). The pharmacotherapeutic modulation of the renal compensatory adaptation is discussed with regard to the stimulation of the tubulosecretory transport of foreign substances with para-amino hippuric acid as principal substance (including own investigations with cyclopenthiazide [Benesal].

Beta-escin is highly effective in reducing postoperative edemas and swellings. It was tried to demonstrate the effect of beta-escin using the thermometry. The temperature of soft tissues and bones can be measured with the help of the thermometry, in this way the circulation of the skin can be determined. In 65 test persons so-called normal thermograms were established, using the infraredthermometer KT 41, which makes registrations without touching the skin. In 53 patients the temperature of the skin was checked after surgery of the hand. 27 patients received beta-escin (Reparil); 26 patients without medication served as controls. In every case the temperature of the operated hand was compared to the other hand. Among the patients, who received escin, the temperature of the operated hand rose for two days following surgery; afterwards it fell quickly. Among the controls the skin-temperature rose up to the 4. day after surgery and decreased slowly. These results demonstrate clearly that after using beta-escin there is a quick reduction of postoperative inflammation and edema.

A dualistic function for the natriuretic ATP.inhibiting factor is formulated on the basis of a phenomenon like compensatory renal adaption of residual nephrons: 1. Support of the tubular sodium excretion to the maintenance of homoeostasis of the organism. 2. Inhibition of the forced up vasodilation of the afferent glomerular vessel. It should suggested that the renal vasoconstrictive effect is a part of a protective system for residual nephrons against the pathogenic hyperfiltration and hyperperfusion.

A multicentric randomised and prospective study on conservative treatment of ureteric calculi had been performed. The frequency and transit time of spontaneously passing of the stones, side effects and cost of treatment have been compared under classic spasmoanalgetic therapy and a phytotherapeutic medicament (Urol). In the group with spasmoanalgetic therapy 85.5% of the stones passed spontaneously, in the group with Urol medication 89.3% of the stones. There was no significant difference concerning the transit time of stones between the two groups, but side effects and costs were less in the Urol-group.

18 persons with unimpaired renal function were examined, if the parenteral application of aescinat was followed by disturbances of renal function. 10 of these persons got for 3 days 10 mg of sodium-aescinat per day administered intravenously. The other test persons got for 6 days 20 mg of aescinat administered. There was no alteration in any of these cases either of serum electrolytes, blood sugar, creatinine, urea, urine analysis, creatinine clearance or hippuran clearance. We come to the conclusion that there has to be a strict indication for the application of aescinat in patients with threatening or apparent renal failure and a cautious dosage on the other hand. Patients with unimpaired renal function can be treated in normal dosage without great danger of renal or other side effects with aescinat for avoiding oedema while passing renal calculi or after plastic surgery.

A saponin complex, isolated from the roots of Polemonium caeruleum L., the aglycones of which are triterpene esters, has been tested for antifungal properties. The blastomycetes Candida tropicalis, Candida albicans and Torulopsis glabrata proved to be very sensitive.