Biomedical subjects

Otto Sticher

Publications and source records attributed to Otto Sticher.

At least 19 recordsLinked to original sources

PubMed2005

A furanocoumarin and polymethoxylated flavonoids from the Yucatec Mayan plant Casimiroa tetrameria.

As part of an ongoing study of the medicinal plants of the Yucatec Maya, Casimiroa tetrameria was investigated for its phytochemistry. From an ethyl acetate partition of an ethanol extract of the leaves, eight flavonoids and a furanocoumarin were isolated and characterised as 5,6,2',3',5',6'-hexamethoxyflavone, 5,6,2',3',6'-pentamethoxyflavone and 5-methoxy-8-(3''-hydroxymethyl-but-2''-enyloxy)-psoralen using a combination of 1H, 13C NMR and NOESY spectroscopy.

Casimiroa↗

PubMed2005

Spasmolytic and antidiarrhoeal properties of the Yucatec Mayan medicinal plant Casimiroa tetrameria.

The Maya of the Yucatán peninsula commonly use the leaves of Casimiroa tetrameria for treating gastrointestinal disorders, notably diarrhoea and dysentery, as well as gastrointestinal cramps. The phytochemical investigation resulted in the isolation of 13 compounds: eight polymethoxylated flavonoids (two as minor components with a main constituent), four flavonoid glycosides and one furanocoumarin. In this study we used two well-established models in order to assess the gastrointestinal effects of C. tetrameria extracts and isolated compounds: the USSING-chamber, a pharmacological model for diarrhoea, and the isolated guinea pig ileum, a model for modulatory effects on ileum contraction. Extracts and the class of polymethoxylated flavonoids showed strong inhibitory effects in both models, which provides ex-vivo evidence for the use of this botanical drug in the treatment of several gastrointestinal problems, most notably diarrhoea. The crude extract, polymethoxylated flavonoid-rich fractions and the polymethoxylated flavonoids tested showed prominent antisecretory activity. Polymethoxylated flavonoid-rich fractions also inhibited the histamine-induced contractions in the guinea pig model. The effects are not due to a single compound, but to a large number of structurally related compounds that all contribute to the effect.

Animals↗

PubMed2004

Phyllanthus piscatorum, ethnopharmacological studies on a women's medicinal plant of the Yanomamï Amerindians.

The shrub Phyllanthus piscatorum Kunth (Euphorbiaceae) is cultivated by various ethnic groups of the Amazon because of its piscicidal properties. During ethnobotanical fieldwork among the Yanomamï Amerindians in Venezuela we observed that Phyllanthus piscatorum was exclusively cultivated and used by the women. Aerial parts of this herbaceous shrub are employed as fish poison and medicine to treat wounds and fungal infections. In addition, the leaves are used as tobacco substitute. Ethnobotanical data regarding the context of the use of this plant are presented. To validate ethnobotanical information related to its medicinal indications, antimicrobial, and antiprotozoal properties of water, methanol (MeOH) and dichloromethane (DCM) extracts were studied. No activity against Gram-positive bacterial strains but significant activity against the fungi Aspergillus fumigatus, Aspergillus flavus and the yeast Candida albicans were found. All extracts showed weak in vitro activity against Plasmodium falciparum and Trypanosoma brucei rhodesiense. The extracts were further investigated for cytotoxic effects in an in vitro test system with leukemia Jurkat T, HeLa, and human peripheral mononuclear blood cells (PBMCs). During the first 48 h the extracts did not exhibit any cytotoxicity. After 72 h the DCM extract potently inhibited viability of HeLa cells. Although in several communities along the upper Orinoco the cultivation and use of Phyllanthus piscatorum is being lost because of the ongoing acculturation, the traditional medicinal use of Phyllanthus piscatorum might provide an effective and cheap remedy against dermatological diseases linked with Candida albicans infections.

Animals↗

PubMed2004

New chromanone acids with antibacterial activity from Calophyllum brasiliense.

Six novel chromanone acids (1-6) were isolated from the bark of Calophyllum brasiliense Cambess. Their structures were elucidated on the basis of 1D and 2D NMR experiments, as well as mass spectrometry. All compounds showed moderate to strong antibacterial activity against Bacillus cereus and Staphylococcus epidermidis, with 1 and 2 being most active. None of the compounds were cytotoxic against KB, Jurkat T, and myosarcoma cancer cells up to 20 microg/mL.

Anti-Bacterial Agents↗

PubMed2003

Influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in Jurkat T cells and human peripheral blood cells: anti-inflammatory and cytotoxic effects.

Sesquiterpene lactones (SLs) are known to have potent anti-inflammatory and cytotoxic properties. So far, the anti-inflammatory effects have mainly been attributed to their inhibition of DNA-binding of the transcription factor NF-kappa B (p65), which is a pivotal regulator of the cellular immune response. Since NF-kappa B is involved in the transcriptional control of several pro-inflammatory and regulatory genes, we investigated the effects of one bifunctional NF-kappa B (p65) inhibiting and two monofunctional NF-kappa B (p65) inactive helenanolide-type SLs on PMA and LPS-induced mRNA expression in CD4(+) Jurkat T and human peripheral blood mononuclear cells (PBMCs) with reverse transcription real-time PCR (RT-rt-PCR). The monofunctional SLs 11 alpha,13-dihydrohelenalin acetate (DHAc) and chamissonolide significantly reduced mitogen-induced cytokine and iNOS mRNA levels in PBMCs and Jurkat T cells at low micromolar concentrations. DHAc also showed significant effects on the gene expression of the house-keeping genes GAP-DH and beta-actin, as well as on NF-ATc, p65, I-kappa B alpha, bcl-2, and cyclin D1. The bifunctional NF-kappa B inhibitor helenalin not only effectively inhibited pro-inflammatory gene expression, but also strongly down-regulated all investigated mRNA levels in a time-dependent manner. Flow cytometry and caspase-8 and -3 assays revealed that helenalin strongly and DHAc moderately induced apoptosis in Jurkat T cells, whereas chamissonolide caused cytoprotective effects. In PBMCs, DHAc and chamissonolide did not inhibit NF-kappa B (p65) DNA-binding at concentrations effective on the transcriptome. Thus, it can be concluded that the biological effects of SLs are not only due to NF-kappa B inhibition, but must be coupled to other mechanisms.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Cytotoxic versus anti-inflammatory effects in HeLa, Jurkat T and human peripheral blood cells caused by guaianolide-type sesquiterpene lactones.

Four guaianolide type sesquiterpene lactones (SL), namely the new 1,2-dihydro-3-oxo-costic acid guaianyl ester 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6beta,12-olide (1) and 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6alpha,12-olide (2), as well as the known moroccolide A [5alphaH-2beta,4-epoxy-3beta-hydroxy-guaia-1(10),11(13)-dien-6beta,12-olide, 3] and 3beta-O-(2-methylbutyryl)-moroccolide A [5alphaH-2beta,4-epoxy-3beta-(2-methylbutyryloxy)-guaia-1(10),11(13)-dien-6beta,12-olide, 4] were examined for their cytotoxic and anti-inflammatory effects in HeLa, Jurkat T and human peripheral blood mononuclear cells. Compounds 1, 2 and 4 were found to exert a strong cytotoxicity similar in potency in all investigated cell types, whereas 3 was significantly less active. Along with the cytotoxic effect compounds 1 and 4 showed a potent and comparable down-regulation of the mRNAs of the house-keeping genes beta-actin and GAP-DH in PBMCs after 20 h. In contrast, the down-regulation of the PMA-induced mRNA levels of the NF-kappaB-driven pro-inflammatory genes IL-2, IL-6, GM-CSF, TNF-alpha, and IL-1beta in PBMCs is significantly stronger with compound 4. Compound 3 did not significantly modulate cytokine mRNAs levels at biochemically relevant concentrations. The electromobility shift assay (EMSA), revealed a stronger inhibition of NF-kappaB for 1 (IC(50) 2.5 microM) than for 4 (IC(50) 5 microM). Both compounds were also subjected to an IL-6 luciferase reporter gene assay and showed IC(50) values of 1.0 (1) and 1.2 microM (4). Thus, the NF-kappaB inhibition measured by EMSA, as well as the IL-6 luciferase assay did not reflect the differential modulation of pro-inflammatory genes measured with RT-rt-PCR.

Animals↗

PubMed2003

Curcumin differentially modulates mRNA profiles in Jurkat T and human peripheral blood mononuclear cells.

Curcumin, the yellow pigment of the rhizome of Curcuma longa is known to inhibit the transcription factors AP-1, Egr-1, NF-kappaB, c-myc and several important signaling kinases. We therefore investigated the differential effects of curcumin in concentation between 1.5 and 13.6 microM on gene expression in T Jurkat CD4(+) and human peripheral blood mononuclear cells (PBMCs). Relative quantification with reverse transcription real-time PCR (RT-rt-PCR) showed that low concentrations of curcumin significantly down-regulated mitogen-induced granulocyte macrophage colony stimulating factor (GM-CSF) mRNA (3- to 5-fold at 3 microM) in a dose- and time-dependent manner in both cell types. In comparison, the down-regulation of inducible nitric oxide (iNOS) mRNA levels was less pronounced, but interferon gamma (IFN-gamma) mRNA was dose-dependently up-regulated with curcumin concentrations up to 8.2 microM. Cyclin D1 mRNA expression was specifically inhibited in Jurkat T cells and stimulated PBMCs. The transcription factors NF-kappaB and NF-ATc were not affected in PBMCs. Interleukin-2 (IL-2), and-6 (IL-6) mRNAs levels were not influenced markedly by curcumin in stimulated PBMCs, but significantly reduced in stimulated Jurkat T cells. In addition, cytotoxic effects and down-regulation of mRNAs, including p65 and the house-keeping genes could only be measured in Jurkat T cells. These findings confirm previous reports on the anti-neoplastic potential of curcumin and show that this compound differentially modulates the expression profile of Th1 cells and PBMCs.

Cell Survival↗

PubMed2003

Acylated flavonoid and phenylethanoid glycosides from Marrubium velutinum.

From the aerial parts of Marrubium velutinum, one acylated flavonoid glycoside, chrysoeriol 7-O-(3",6"-di-O-E-p-coumaroyl)-beta-D-glucopyranoside, and two tetrasaccharidic phenylethanoid glycosides, velutinosides I-II, have been isolated together with ten known flavonoids and seven known phenylethanoid glycosides. The structures of the isolated compounds were established by means of NMR, MS, and UV spectral analyses.

Acylation↗

PubMed2003

Antiquity of medicinal plant usage in two Macro-Mayan ethnic groups (México).

In the biological sciences the use of medicinal plants in indigenous cultures is commonly seen as being based on a long tradition ('traditional medicine'). However, under normal circumstances, ethnobotanical studies cannot provide evidence on the antiquity of specific uses for medicinal plants since oral traditions have a limited historical depth and archaeological evidence does not provide evidence for the specific medicinal use of a certain plant. Here, we provide evidence for the antiquity of medicinal plant use in the Olmec region in Mexico by comparing the pharmacopoeias of the linguistically related Lowland Mixe and Zoque-Popoluca. These cultures, separated for about 2000 years, have cognates for vernacular medicinal plant names in common. For fifteen species such cognate names were detected. Also, a statistically significant segment of the medicinal flora is used for similar purposes. Overall, 123 species are shared between the two groups and of these 62 have a similar usage. In nine cases they also have a similar name. These findings make a transmission of such knowledge since the time of the Olmecs highly likely.

History, 20th Century↗

PubMed2003

New stigmastane sterols from Ajuga salicifolia.

A new sterol, ajugasalicigenin (1), and three new sterol glycosides, ajugasaliciosides F-H (2-4), were isolated and characterized from the aerial parts of Ajuga salicifolia. Compounds 1-4 are further representatives of the stigmastane type of sterols. Their cytotoxicity against KB (HeLa) and Jurkat T cancer cells was evaluated.

Ajuga↗

PubMed2003

New cytotoxic sesquiterpene lactones from Warionia saharae.

Cytotoxicity-guided fractionation of the methanol soluble part of the dichloromethane extract of the leaves of Warionia saharae led to the isolation of the two new guaianolide-type sesquiterpene lactones, 5 alpha H-3 beta,4 beta-epoxy-14-oxo-guaia-1(10),11(13)-dien-6 alpha,12-olide (1), 5 alpha H-2 beta,4 beta-epoxy-3 alpha-hydroxy-guaia-1(10),11(13)-dien-6 alpha,12-olide (6), and the new eudesmane type sesquiterpene 1 beta,6 alpha-dihydroxycostic acid ( 4). In addition, the known sesquiterpene lactones 5 alpha H-2 beta-hydroxyguaia-3(4),10(14),11(13)-trien-6 alpha,12-olide (2), reynosin (3), 5 alpha H-1 alpha,10 alpha:3 alpha,4 alpha-diepoxyguaia-11(13)-en-6 alpha,12-olide (5), and dehydroleucodin (7) were isolated together with the known flavone hispidulin. Cytotoxicity testing of the sesquiterpene lactones against the KB cancer cell line (ATCC CCL17) revealed IC50 values of 3.5 (1), 2.6 ( 2), 2.7 ( 3), 4.3 ( 5), 3.6 ( 6), and 1.3 (7) microg/mL. Compound 4 was not active up to 20 microg/mL.

Antineoplastic Agents↗

PubMed2003

Antifungal, antiprotozoal, cytotoxic and piscicidal properties of Justicidin B and a new arylnaphthalide lignan from Phyllanthus piscatorum.

Using activity against Candida albicans as a lead, the bioactivity-guided fractionation of the dichloromethane extract of Phyllanthus piscatorum led to the isolation of the arylnaphthalide lignan justicidin B (1), which was found to be present in high amounts, and a new C-11 hydroxylated derivative that we named piscatorin (2). We provide evidence that justicidin B (1) is the main active principle of P. piscatorum, showing the same biological effects that were found for the raw extracts. Justicidin B inhibited the growth of the pathogenic fungi Aspergillus fumigatus (MIC > or = 1 microg/mL), Aspergillus flavus (MIC > or = 12 microg/mL), and Candida albicans (MIC > or = 4 microg/mL), but was not effective against Cryptococcus neoformans and Blastoschizomyces capitatus. Justicidin B also exhibited strong activity against the trypomastigote form of Trypanosoma brucei rhodesiense (IC50 = 0.2 microg/mL) and moderate activity against Trypanosoma cruzi (IC50 = 2.6 microg/mL). Testing against Plasmodium falciparum showed only weak activity. This is the first report on the in vitro fungicidal and antiprotozoal effects of justicidin B. In addition, both compounds exhibited a non-specific cytotoxicity in neoplastic and primary cell cultures. No antibacterial effects were detected. Both compounds were piscicidal against zebra fish and it is shown for the first time that piscatorin (2) and justicidin B (1) are the piscicidal principles of P. piscatorum, exhibiting a potency that is comparable to rotenone.

Animals↗

PubMed2002

Quinolizidine alkaloids from the curare adjuvant Clathrotropis glaucophylla.

The bark of Clathrotropis glaucophylla (Fabaceae) is used as admixture of curare arrow poison by the Yanomami; Amerindians in Venezuela. A new quinolizidine alkaloid (QA), (-)-13alpha-hydroxy-15alpha-(1-hydroxyethyl)-anagyrine [(-)-clathrotropine], was isolated from the alkaloid extract of C. glaucophylla bark, together with eleven known QAs: (-)-anagyrine, (-)-thermopsine, (-)-baptifoline, (-)-epibaptifoline, (-)-rhombifoline, (-)-tinctorine, (-)-cytisine, (-)-N-methylcytisine, (-)-lupanine, (-)-6alpha-hydroxylupanine and (+)-5,6-dehydrolupanine. The isolation and structure elucidation were performed with the aid of chromatographic (TLC, HPLC and CC) and spectroscopic (UV and 1D/2D NMR) methods, and mass spectrometry. To our knowledge, this is the first time quinolizidine alkaloids have been isolated from an arrow poison ingredient. It is also the first report on Clathrotropis species being used for preparation of arrow poison.

Alkaloids↗

PubMed2002

Yucatec Mayan medicinal plants: evaluation based on indigenous uses.

As part of an ethnopharmacological field study 48 medicinal plants were evaluated using several biological assays with the goal to obtain information on the pharmacological effects of these plants, which may be of direct relevance to the indigenous uses. Three species used to treat gastrointestinal disorders showed remarkable activity against Helicobacter pylori. One of them showed activity against Giardia duodenalis. Cytotoxic effects against KB cells were found for six species. In the group of plants used for dermatological conditions several species were active against gram-positive bacteria and Candida albicans. Two plant species of this group were found to be active in an Nuclear Factor-kappaB (NF-kappaB) assay measuring inhibition of this pro-inflammatory transcription factor. A species of the Solanaceae, applied in cases of pain and fever, showed a weak activity against Plasmodium falciparum. One species traditionally used for diabetes exhibited antihyperglycemic activity. None of the six species from the group of 'women's medicine' showed relevant affinity to the D(2) dopamine receptor. Based on this evaluation, plants with strong activities should be further investigated phytochemically and pharmacologically to identify active fractions and compounds.

Animals↗

PubMed2002

Medicinal plants of the Popoluca, México: organoleptic properties as indigenous selection criteria.

The taste and smell of the environment are important to humans in everyday life and are of particular relevance for the selection of medicinal versus non-medicinal plant species. In a 16-months study with the Popoluca of southern Veracruz (Mexico), we focused on the indigenous selection criteria for medicinal plants. We provide evidence for a highly significant association between organoleptic properties of plants and the use of these species as medicine. Additionally, the doctrine of signature is an essential mnemonic aid, which facilitates remembering the use assigned to the plant. From the Popoluca point of view, it is essential to find substitutes or alternative treatments when a certain species is not at hand. We show that organoleptic properties and the doctrine of signature are excellent guides for selecting or memorising such medicinals.

Color↗

PubMed2002

Evaluation of glucoiberin reference material from Iberis amara by spectroscopic fingerprinting.

Increasing worldwide regulations require increased efforts toward validation of analytical and pharmacological reference materials. A detailed survey of glucoiberin, a prototype lead constituent of therapeutic value, using 1D/2D NMR, MS, and X-ray spectroscopy provided precise phytochemical data for structure assignment. Quantitative reference validation was achieved by the recently proposed qNMR method.

Choline↗

PubMed2002

New cytotoxic 6,7-cis and 6,7-trans configured guaianolides from Warionia saharae.

Using cytotoxicity against the KB cancer cell line (ATCC CCL17) as a lead, bioactivity-guided fractionation of the MeOH-soluble part of the DCM extract of Warionia saharae leaves led to the isolation of six new cytotoxic guaianolide type sesquiterpene lactones (1-6). Besides two guaianolides showing the common 6,7-trans fused lactone ring (3 and 4), four compounds exhibiting the more rare 6,7-cis configuration (1,2 and 5,6) were also isolated. Compounds 1, 2, 5, and 6 showed an unprecedented ether bridge between C-2 and C-4. The structures were deduced from extensive 1D and 2D NMR spectroscopy ((1)H, (13)C, DQF-COSY, HSQC, HMBC, ROESY), as well as mass spectrometry (EI and HR-MALDI). Cytotoxicity testing against the KB cancer cell line revealed IC(50) values of 1.0 (1), 4.5 (2), 1.7 (3), 2.0 (4), 3.3 (5), and 5.5 (6) microg/mL.

Antineoplastic Agents, Phytogenic↗

PubMed2002

Oxidation products of abietic acid and its methyl ester.

Abietic acid (1) and its methyl ester (2) were investigated under various storage conditions to provide an indication of their preferred oxidation mechanisms and to investigate the most susceptible positions for modification in the abietane skeleton. Six known compounds, methyl 7alpha,13beta-dihydroxyabiet-8(14)-enoate (4a), methyl 7alpha,13alpha-dihydroxyabiet-8(14)-enoate (4b), methyl 12-oxoabietate (6), methyl 7-oxodehydroabietate (7), methyl 7alpha-hydroxydehydroabietate (8), and 13,14-seco-13,14-dioxoabiet-7(8)-enoic acid (11), were identified. Compounds 7 and 8 are regarded as potent allergens. In addition, six new oxidation products were isolated, methyl 13beta-ethoxy-7alpha-hydroxyabiet-8(14)-enoate (3a), methyl 13alpha-ethoxy-7alpha-hydroxyabiet-8(14)-enoate (3b), methyl 7alpha-hydroperoxy-13alpha-hydroxyabiet-8(14)-enoate or methyl 13alpha-hydroperoxy-7alpha-hydroxyabiet-8(14)-enoate (5), 7alpha,13beta-dihydroxyabiet-8(14)-enoic acid (9a), 7alpha,13alpha-dihydroxyabiet-8(14)-enoic acid (9b), and 7alpha,15-dihydroxydeydroabietic acid (10). Their structures were characterized on the basis of spectroscopic data interpretation. The cytotoxicity of several compounds against KB cells was evaluated, and weak activity was observed for 6, 7, and 8 with IC(50) values of 12.5, 4.5, and 5.8 microg/mL, respectively.

Abietanes↗