The use of preparations from
Bryophyllum pinnatum in tocolysis is supported by both clinical (retrospective comparative studies) and experimental (using uterus strips) evidence. We studied here the ...effect of
B. pinnatum juice on the response of cultured human myometrial cells to stimulation by oxytocin, a hormone known to be involved in the control of uterine contractions by increasing the intracellular free calcium concentration (Ca
2+
i).
In this work, Ca
2+
i was measured online during stimulation of human myometrial cells (hTERT-C3 and M11) with oxytocin, which had been pre-incubated in the absence or in the presence of
B. pinnatum juice. Since no functional voltage-gated Ca
2+ channels could be detected in these myometrial cells, the effect of
B. pinnatum juice was as well studied in SH-SY5Y neuroblastoma cells, which are known to have such channels and can be depolarised with KCl.
B. pinnatum juice prevented the oxytocin-induced increase in Ca
2+
i in hTERT-C3 human myometrial cells in a dose-dependent manner, achieving a ca. 80% inhibition at a 2% concentration. Comparable results were obtained with M11 human primary myometrial cells. In hTERT-C3 cells, prevention of the oxytocin-induced increase in Ca
2+
i was independent of the extracellular Ca
2+ concentration and of voltage-dependent Ca
2+-channels.
B. pinnatum juice delayed, but did not prevent the depolarization-induced increase in Ca
2+
i in SH-SY5Y cells.
Taken together, the data suggest a specific and concentration-dependent effect of
B. pinnatum juice on the oxytocin signalling pathway, which seems to corroborate its use in tocolysis. Such a specific mechanism would explain the rare and minor side-effects in tocolysis with
B. pinnatum as well as its high therapeutic index.
The future of natural product-based drug discovery critically depends on efficient and targeted approaches for early compound identification and dereplication. For that purpose we have established a ...technology platform combining pre-formatted extract libraries with a miniaturized and highly effective approach termed HPLC-based activity profiling. The flexibility of our platform enables discovery projects to be conducted in decentralized collaborative settings.
In a collaboration with pharmacologists at the University of Vienna we have been screening for GABA
A
receptor modulatory properties in an extract library of traditional medicinal plants. We identified a spectrum of compounds with scaffolds that are new for the target. Selected compounds and their
in vitro
and
in vivo
pharmacological characterization will be presented. The development of the GABA
A
receptor modulator piperine into a non-TRPV1 activating lead SCT-66 will be highlighted.
Neglected infectious diseases constitute a major health problem affecting over 800 million people worldwide. Natural products such as quinine and artemisinine have been essential for the development of effective anti-protozoan treatments. In a collaboration with the Swiss Tropical and Public Health Institute we have been pursuing natural product based lead discovery against protozoan diseases. HPLC-based activity profiling led to identification of numerous active molecules belonging to different compound classes. The discovery of cynaropicrin as the first plant metabolite with
in vivo
activity in the
T. brucei rhodesiense
STIB 900 acute mouse model will be highlighted, and results from mechanistic studies with the compound will be discussed.
(
E,
Z)-3-(3′,5′-Dimethoxy-4′-hydroxy-benzylidene)-2-indolinone (indolinone) is an alkaloid that has been identified as a pharmacologically active compound in extracts of the traditional ...anti-inflammatory herb
Isatis tinctoria. Indolinone has been shown to inhibit compound 48/80-induced mast cell degranulation in vitro. Application of indolinone to bone marrow derived mast cells showed that it was uniformly distributed in the cytoplasm and that cellular uptake was terminated within minutes. Pre-treatment of IgE-sensitized mast cells with 100
nM indolinone rendered them insensitive against FcɛRI-receptor dependent degranulation. However, upstream signalling induced by antigen such as activation of PI3-K and MAPK remained unaffected. We conclude that indolinone blocks mast cell degranulation at the level of granule exocitosis with an IC
50 of 54
nm.
Various extracts prepared from the traditional dye and medicinal plant Isatis tinctoria L. were submitted to a broad in vitro screening against 16 anti-inflammatory targets. Dichloromethane (DCM) ...extracts from dried leaves showed a marked cyclooxygenase (COX) inhibitory activity with a preferential effect on COX-2 catalysed prostaglandin synthesis. A supercritical fluid extraction (SFE) procedure employing CO2-modifier mixtures was developed by which the bioactivity profile and chromatographic fingerprint of the DCM extract could be reproduced. High-resolution activity directed on-line identification of the COX-2 inhibitory principle, using a combination of LC-DAD-MS with a microtitre-based bioassay, led to the identification of tryptanthrin (1) as the constituent responsible for essentially all COX-2 inhibitory activity in the crude extract. Following on-line identification, 1 was isolated at preparative scale and its structure confirmed by comparison with synthetic tryptanthrin. In an assay with lipopolysaccharide stimulated Mono Mac 6 cells, tryptanthrin (1) was of comparable potency (IC50 = 64 nM) than the preferential COX-2 inhibitors nimesulide (IC50 = 39 nM) and NS 398 (IC50 = 2 nM). The SFE extract and 1 showed no cytotoxicity in Mono Mac 6 and RAW 264.7 cells when tested at 100 microg/ml and 10 microM, respectively.
The syphilis epidemic among men who have sex with men (MSM) in major US cities and concomitant increases in high-risk sexual behavior, have raised concerns of increased HIV transmission in this ...population. Therefore, to provide information for health promotion and disease awareness efforts, we investigated sexual behaviors, partner selection preferences and HIV serostatus disclosure practices of MSM at the White Party in Palm Springs, California. Circuit party attendees reported engaging in unprotected anal sex, however, a high proportion reported disclosing their HIV status. These findings suggest that some gay men are serosorting as a risk reduction strategy or implementing sexual risk reduction strategies to protect themselves and their partners. In our study, HIV-negative men were nine times more likely to report a preference for a seroconcordant sexual partner. The self-protecting attitudes of HIV-negative men in our sample outweighed the partner-protecting attitudes of HIV-positive men. This suggests that prevention interventions focusing on HIV-positive persons are warranted.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Numerous wild plants have been used as foods in the past by local Alpine populations. Most of these have fallen into oblivion, and very little is known about their constituents and biological ...properties. We recently initiated a project to identify forgotten plants which could potentially be taken into cultivation and re-established as food plants with interesting sensory properties and a phytochemical composition which might have beneficial effects on health. Based on an ethnobotanical survey in the Lower Valais region, and on considerations concerning the feasibility of large scale cultivation, the round-headed rampion (Phyteuma orbiculare, Campanulaceae), a perennial herb that was eaten in the past as a salad, was selected for a detailed phytochemical investigation. Different extracts of the aerial parts were submitted to a comprehensive metabolite profiling using a combination of TLC, HPLC-UV, HPLC-MS and off-line microprobe NMR analysis. Various secondary metabolites including saponins and flavonoids were detected in the aerial parts of P. orbiculare, and two saponins with structurally unique aglycons were isolated and characterized. Preliminary data on nutritionally valuable substances such as carotenes and fatty acids were obtained for a specimen collected near Orsières (Valais). Further investigations on samples collected at different locations and at various vegetation stages are planned.
The antiplasmodial, anti-trypanosomal and anti-leishmanial activity of 25 plant extracts obtained from seven Tanzanian medicinal plants: Annickia (Enantia) kummeriae (Annonaceae), Artemisia annua ...(Asteraceae), Pseudospondias microcarpa (Anacardiaceae), Drypetes natalensis (Euphorbiaceae), Acridocarpus chloropterus (Malpighiaceae), Maytenus senegalensis (Celastraceae) and Neurautanenia mitis (Papilonaceae), were evaluated in vitro against Plasmodium falciparum K1, Trypanosoma brucei rhodesiense STIB 900 and axenic Leishmania donovani MHOM-ET-67/82. Out of the 25 extracts tested, 17 showed good antiplasmodial activity (IC50 0.04-5.0 microg/ml), 7 exhibited moderate anti-trypanosomal activity (IC50 2.3-2.8 microg/ml), while 5 displayed mild anti-leishmanial activity (IC50 8.8-9.79 microg/ml). A. kummeriae, A. annua, P. microcarpa, D. natalensis, M. senegalensis and N. mitis extracts had good antiplasmodial activity (IC50 0.04-2.1 microg/ml) and selectivity indices (29.2-2,250 microg/ml). The high antiplasmodial, moderate anti-trypanosomal and mild anti-leishmanial activity make these plants good candidates for bioassay-guided isolation of anti-protozoal compounds which could serve as new lead structures for drug development.
A selection of 32 fungal strains, belonging to 8 genera of entomopathogenic Deuteromycetes collected in various provinces of China, were screened for activities on targets involved in degenerative ...diseases of the central nervous system. The strains were grown under various fermentation conditions, and a total of 256 different extracts were obtained. The bioassays included functional screens for NMDA antagonistic activity in stably transfected fibroblasts, for neuritogenic activities in PC-12 cells, and tests for MAO inhibitory and radical scavenging properties. Several extracts with promising activities were identified. Some
Paecilomyces extracts induced pronounced axonal-like outgrowths in PC-12 cells. In
Paecilomyces militaris RCEF 0095, the neuritogenic activity could be linked to yellow pigments. Three
Beauveria and
Paecilomyces strains showed radical scavenging properties, which could be localized in the extract by a bioautographic assay on TLC. An extract obtained from the mycelium of
Paecilomyces tenuipes RCEF 0275 showed moderate MAO inhibitory activity, whereas extracts of
Sporothrix chondracris RCEF 0187 antagonized NMDA receptor mediated cell toxicity.
The pungent principles and the essential oil from the pericarp of Zanthoxylum schinifolium (Rutaceae) have been investigated and compared to those of Z. bungeanum, the primary source of the ...traditional Chinese drug Huajiao (Pericarpium Zanthoxyli). HPLC-MS and HPLC-NMR
analyses revealed an alkylamide profile highly similar to that of Z. bungeanum, with hydroxy-α-sanshool and hydroxy-β-sanshool being in both plants the major constituents of the alkylamide fraction. GC-FID and GC-MS analyses of the essential oil showed that limonene was,
like in Z. bungeanum, the main component (21%), followed by 4-terpineol, γ-terpinene, α-terpineol acetate, β-pinene, α-terpineol and β-linalool.
The red palm weevilRhynchophorus ferrugineus (Olivier) (RPW) is the most serious pest of date palms in the Middle East. Weevil infestation was first detected in Israel in the summer of 1999 in date ...plantations in the Jordan Valley, on the west bank of the Jordan River and in the northern area of the Dead Sea. For 2 years following the discovery of the pest, prophylactic insecticide chemical treatments as well as adult weevil trapping were carried out over 450 ha of date palm plantations. Traps loaded with a commercial aggregation pheromone, ferrugineol, supplemented with ethyl acetate and a fermenting mixture of dates and sugarcane molasses, were posted in high trap density (approx. ten traps per ha) in order to monitor weevil infestation and reduce the RPW population by mass trapping. A significant decrease in number of trapped beetles and infested trees was observed in 2001 and continued in the following years. No infested trees have been found since 2002, indicating a decrease in RPW population. The sex ratio of trapped adults during 3 years of study was significantly female-biased (∼2.5:1). Therefore, mass trapping might have played a significant role in the suppression of RPW populations in date plantations.
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