RESUMO
The antiplasmodial active extract of Xanthium cavanillesii contains 3,4-dicaffeoyl quinic acid (3,4-DCQA), 3,5-dicaffeoyl quinic acid (3,5-DCQA) and 1,3,5-tricaffeoyl quinic acid (1,3,5-TCQA). These results inspired us to investigate the interaction of these molecules with a promising validated target of Plasmodium, PfATP6 orthologue of mammalian Ca+2-ATPase. Models of this receptor were obtained through comparative modelling. Afterwards, molecular docking studies were used to identify possible interaction modes of these caffeoyl quinic derivatives on the binding site. The 1,3,5-TCQA had the best energy, but all of these had better energy than thapsigargin, a non-competitive inhibitor of the sarco/endoplasmatic reticulum Ca+2-ATPase (SERCA).
Assuntos
Antimaláricos/farmacologia , Frutas/química , Extratos Vegetais/farmacologia , Ácido Quínico/análogos & derivados , Xanthium/química , Animais , Antimaláricos/química , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Plasmodium/efeitos dos fármacos , Ácido Quínico/química , Ácido Quínico/farmacologia , Tapsigargina/farmacologiaRESUMO
In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-ß1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-ß1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-ß1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-ß1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-ß1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.
Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Pulmão/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fator de Crescimento Transformador beta1/imunologia , Remodelação das Vias Aéreas/efeitos dos fármacos , Animais , Antiasmáticos/isolamento & purificação , Asma/induzido quimicamente , Asma/imunologia , Asma/patologia , Berberidaceae/química , Dexametasona/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Elaeagnaceae/química , Ephedra/química , Regulação da Expressão Gênica , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Ovalbumina , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Scutellaria baicalensis/química , Transdução de Sinais , Proteína Smad3/genética , Proteína Smad3/imunologia , Proteína Smad7/genética , Proteína Smad7/imunologia , Fator de Crescimento Transformador beta1/genética , Xanthium/químicaRESUMO
The leaves of the Xanthium spinosum plant have been used culturally in Paraguay for their medicinal properties. Acute toxicity of mature leaf extract was evaluated. For the study, 35 Balb/c mice were selected and allocated into 7 groups, 6 test groups and 1 control group. The extract was prepared in concentrations of 6% and 9% (g/dL). The 6% concentration was administrated to 3 test groups and 9% concentration to the remaining 3 groups, with doses between 200 and 1000 mg/kg per mouse. After 14 days of observation, blood samples were taken for laboratory studies of urea and transaminases and organs were examined for pathological studies. There were increased levels of GOT and urea in the test groups compared to the control group. In conclusion, the consumption of mature leaf extract of Xanthium spinosum can cause hepatic damage.
Assuntos
Extratos Vegetais/toxicidade , Xanthium/química , Animais , Doença Hepática Induzida por Substâncias e Drogas , Camundongos , Camundongos Endogâmicos BALB C , Folhas de PlantaRESUMO
The sesquiterpene lactones xanthanodiene, 4-epi-xanthanol, 4-epi-isoxanthanol, and 4-epi-xanthinin, as well as the xanthanolide derivative 4-oxo-bedfordia acid were isolated from the chloroform extracts of roots and flowers of Xanthium cavanillesii Schouw. The identities of these compounds were corroborated through comparison of their spectroscopic data, including IR, MS, and (1)H and (13)C NMR assignments, with literature reports. In addition, the structural characterization of 4-oxo-bedfordia acid was revisited and a comprehensive spectroscopic study of the compound is presented. This is to our knowledge the first phytochemical investigation of the roots of X. cavanillesii, and of flowers in the whole Xanthium genus.
Assuntos
Sesquiterpenos/isolamento & purificação , Xanthium/química , Flores/química , Espectroscopia de Ressonância Magnética , Raízes de Plantas/química , Sesquiterpenos/químicaRESUMO
Xanthium strumarium L. is a member of the Asteraceae commonly used in Cuba, mainly as diuretic. Some toxic properties of this plant have also been reported and, to date, very little is known about its genotoxic properties. The present work aims was to evaluate the potential cytotoxic and genotoxic risk of whole extract from Xanthium strumarium L. whole extract of aerial parts. No positive response was observed in a battery of four Salmonella typhimurium strains, when exposed to concentrations up to 5 mg/plate, with and without mammalian metabolic activation (liver microsomal S9 fraction from Wistar rats). In CHO cells, high concentrations (25-100 µg/mL) revealed significant reduction in cell viability. Results from sister chromatid exchanges, chromosome aberrations, and comet assay showed that X. strumarium extract is genotoxic at the highest concentration used, when clear cytotoxic effects were also observed. On the contrary, no increase in micronuclei frequency in bone marrow cells was observed when the extract was orally administered to mice (100, 500, and 2000 mg/Kg doses). The data presented here constitute the most complete study on the genotoxic potential of X. strumarium L. and show that the extract can induce in vitro DNA damage at cytotoxic concentrations.
Assuntos
Dano ao DNA/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Animais , Células CHO , Cricetulus , Camundongos , Extratos Vegetais/química , Ratos , Salmonella typhimurium/efeitos dos fármacos , Xanthium/químicaRESUMO
The main objective of anti-carcinogenic chemotherapy is to stop uncontrolled cellular proliferation. This has prompted us to begin a systematic survey of new effective inhibitors with ability to react with cytoskeletal components and arrest living, dividing cells. Even for traditional populations herbs-consuming, encouraging the use of species with chemopreventive actions could be helpful as part of life expectancy improvement strategies. Herbal products have significantly lower costs, exhibit little or no toxicity during long-term oral administration and are relatively available at large scale. Current work involved the screening of 85 extracts from Cuban medicinal plants, selected on the basis of traditional use, ethnobotanics and pharmacological information (antiparasitic, antitumour, abortive, etc.). Antitubulinic activity in the hydroalcoholics extracts was evaluated by using a modified version of the conventional turbidity assay of tubulin assembly/ disassembly. The activity limits of the news isolated antitubulin agents were thoroughly investigated. According to the presented results, the extracts displaying the highest antitubulinic activity were Tamarindus indica L., Lawsonia inermes L and Xanthium strumarium L.
Detener la proliferación celular es el principal propósito de la quimioterapia anticarcinogénica. Para ello se ha realizado una búsqueda a partir de fuentes naturales de nuevos inhibidores efectivos que reaccionen con los componentes del citoesqueleto y puedan detener la división celular. En poblaciones que tradicionalmente utilizan plantas medicinales se estimula el uso de aquellas especies con acción quimiopreventivas como parte de una estrategia que contribuya a la calidad de vida. Los productos herbarios tienen costos significativamente más bajos, exhiben poca o ninguna toxicidad durante la administración oral a largo plazo y están al alcance de todos. Nuestro trabajo consistió en realizar un tamizaje de 85 extractos de plantas medicinales cubanas seleccionadas en base al uso tradicional, en las encuestas etnobotánicas e información farmacológica (actividad antiparasitaria, antitumoral, abortiva, etc). La actividad antitubulínica fue evaluada mediante una versión modificada del ensayo turbimétrico del ensamblaje/desensamblaje de la tubulina. Se determinó la actividad límite de los nuevos agentes antitubulínicos siendo los extractos de Tamarindus indica L., Lawsonia inermes L and Xanthium strumarium L. los de mejor actividad antitubulínica según las condiciones ensayadas.
Assuntos
Antimitóticos/farmacologia , Extratos Vegetais/farmacologia , Plantas/química , Antineoplásicos/farmacologia , Cuba , Flora , Lawsonia (Planta)/química , Microtúbulos , Preparações de Plantas/farmacologia , Tamarindus/química , Xanthium/químicaRESUMO
In vitro screening of the dichloromethane extracts of 16 Asteraceae species native to Sudan for activity against major protozoan pathogens revealed that a Xanthium brasilicum Vell. [syn. X. strumarium var. brasilicum (Vell.) Baker in Mart.] extract was the most active against Trypanosoma brucei rhodesiense, the etiological agent of East African human trypanosomiasis (IC(50) = 0.1 microg/mL). This plant extract also exhibited noticeable activities against T. cruzi (Chagas disease), Leishmania donovani (Kala-Azar) as well as Plasmodium falciparum (Malaria tropica). Bioactivity-guided fractionation resulted in the isolation of four bioactive sesquiterpene lactones (STL) of the xanthanolide series (4,5-seco-guaianolide-type). They were identified by spectroscopic means as 8-epixanthatin (1), 8-epixanthatin 1beta,5beta-epoxide (2), and as the dimers pungiolide A (4) as well as pungiolide B (5). Two further modified xanthanolide sesquiterpene lactones, xanthipungolide (3) and 4,15-dinor-1,11(13)-xanthadiene-3,5beta:12,8beta-diolide (6) were isolated. While xanthipungolide turned out to be inactive against the tested parasites, the dinor-xanthanlide showed significant activity against T. brucei rhodesiense and L. donovani. All isolated compounds were previously known from other Xanthium species but this is the first report on their occurrence in X. brasilicum, and, most notably, on their antiprotozoal activity. As the most active single compound from this extract, 8-epixanthatin 1beta,5beta-epoxide showed IC(50) values of 0.09, 2.95, 0.16 and 1.71 microg/mL (0.33, 11.3, 0.6 and 6.5 microM) against T. brucei rhodesiense, T. cruzi, L. donovani and P. falciparum, respectively, while its cytotoxicity against rat myoblast cells used as control was determined at 5.8 microg/mL (22.1 microM). Besides assessment of their antiprotozoal activity, the structural assignments for the dimeric xanthanolides pungiolide A and B were reinvestigated and fully established.
Assuntos
Antiprotozoários/farmacologia , Asteraceae/química , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Xanthium/química , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Células Cultivadas , Fracionamento Químico , Concentração Inibidora 50 , Lactonas/química , Lactonas/isolamento & purificação , Leishmania donovani/efeitos dos fármacos , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Ratos , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Development of new antimicrobial compounds against different microorganisms is becoming critically important, as infectious diseases are still one of the leading causes of death in the world. The pharmaceutical industry is searching for new lead compounds with novel chemical structures to overcome the increasing resistance to known antibiotics. Plants can be a useful source of these lead compounds. Xanthium cavanillesii Schouw, Asteraceae, grows wild in Uruguay and its infusion is used in traditional medicine as a skin antiseptic. We have previously reported studies on the antimicrobial activity of several extracts of X. cavanillesii against different microorganisms. In this work, we present the isolation and structural elucidation by spectroscopical methods of a sesquiterpene lactone with a new xanthanolide derived skeleton.
Assuntos
Lactonas/química , Extratos Vegetais/química , Xanthium/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Cromatografia Gasosa , Lactonas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , UruguaiRESUMO
This study describes the development and validation of a method for quantification of the antiulcer experimental drug xanthatin in tablets by capillary electrophoresis (CE). Solid oral dosage forms based on xanthatin were designed and assayed on rats. A CE methodology was developed; the parameters evaluated were: background electrolyte composition, concentration and pH, applied voltage and sample preparation. The method was validated in terms of range of linearity, limits of detection (LOD) and quantification (LOQ), accuracy, precision and selectivity and then applied to the pharmaceutical dosage forms. Xanthatin determination was carried out in less than 3 min with a 20 mM sodium tetraborate buffer, pH 9.20. Drug concentration per tablet found was 2.97 +/- 0.2 mg. Calibration plots were linear over at least three orders of magnitude of analyte concentrations, LOD and LOQ were 7.6 and 26 microg mL(-1) respectively. For accuracy evaluation a recovery test was performed, the values being better than 98.6%. With respect to precision, the results obtained were better than 1.02 RSD% (repeatability) and 1.54% (intermediate precision). After the manufacturing process the resulting tablets were biologically active. The methodology developed is useful, simple and rapid for xanthatin determination in tablets.
Assuntos
Antiulcerosos , Furanos/análise , Xanthium/química , Fenômenos Químicos , Físico-Química , Eletroforese Capilar , Etanol , Furanos/isolamento & purificação , Furanos/farmacologia , Indicadores e Reagentes , Controle de Qualidade , Reprodutibilidade dos Testes , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , ComprimidosRESUMO
The preventive effect of natural xanthanolides as well as a series of synthetic derivatives on ulcer formation induced by absolute ethanol in rats was examined. Among the compounds tested, xanthatin gave the strongest protective activity. The inhibitory action exerted by this molecule on the lesions induced by 0.6N HCl and 0.2N NaOH was highly significant, reducing ulceration in the range of 58-96% at a dose from 12.5 to 100mg/kg. These results appear to confirm that the presence of a non-hindered alpha,beta-unsaturated carbonyl group seems to be an essential structural requirement for the gastric cytoprotective activity of these compounds. In order to explore this possibility, a theoretical conformational analysis was performed. We suggest that the mechanism of protection would involve, at least in part, a nucleophylic attack of the sulfhydryl group from the biological molecules present in the gastric mucosa to electrophylic carbons accessible in suitable Michael acceptors.