RESUMEN
Metabolomic profiles were explored to understand environmental and taxonomic influences on the metabolism of two congeneric zoanthids, Palythoa caribaeorum and P. variabilis, collected across distinct geographical ranges. Integrated mass spectrometry data suggested the major influence of geographical location on chemical divergence when compared to species differentiation.
Asunto(s)
Antozoos/química , Antozoos/metabolismo , Metabolómica , Animales , Brasil , Geografía , Espectrometría de Masas , Estructura Molecular , Especificidad de la EspecieRESUMEN
The use of natural products in therapeutics has been growing over the years. Lignans are compounds with large pharmaceutical use, which has aroused interest in the search for new drugs to treat diseases. The present study evaluated the cytotoxicity of (-)-trachelogenin, a dibenzylbutyrolactone type lignan isolated from Combretum fruticosum, against several tumor and non-tumor cell lines using the MTT assay and its possible mechanism of action. (-)-Trachelogenin showed IC50 values ranging of 0.8-32.4µM in SF-295 and HL-60 cell lines, respectively and IC50 values >64µM in non-tumor cell lines. (-)-trachelogenin persistently induced autophagic cell death, with cytoplasmic vacuolization and formation of autophagosomes mediated by increasing LC3 activation and altering the expression levels of Beclin-1.
Asunto(s)
4-Butirolactona/análogos & derivados , Antineoplásicos Fitogénicos/farmacología , Autofagia/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Combretum/química , Descubrimiento de Drogas , Tallos de la Planta/química , 4-Butirolactona/efectos adversos , 4-Butirolactona/química , 4-Butirolactona/aislamiento & purificación , 4-Butirolactona/farmacología , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Autofagosomas/efectos de los fármacos , Autofagosomas/patología , Beclina-1/agonistas , Beclina-1/metabolismo , Brasil , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/patología , Combretum/crecimiento & desarrollo , Etnofarmacología , Células HCT116 , Humanos , Concentración 50 Inhibidora , Medicina Tradicional , Proteínas Asociadas a Microtúbulos/agonistas , Proteínas Asociadas a Microtúbulos/metabolismo , Estructura Molecular , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/metabolismo , Tallos de la Planta/crecimiento & desarrollo , Vacuolas/efectos de los fármacos , Vacuolas/patologíaRESUMEN
The anti-inflammatory effect of physalin E, a seco-steroid isolated from Physalis angulata L. was evaluated on acute and chronic models of dermatitis induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and oxazolone, respectively, in mouse ear. The changes in ear edema/thickness, production of pro-inflammatory cytokines (TNF-alpha and IFN-gamma), myeloperoxidase (MPO) activity, and histological and immunohistochemical findings were analysed, as indicators of dermal inflammation. Similar to dexamethasone, topically applied Physalin E (0.125; 0.25 and 0.5 mg/ear) potently inhibited the TPA and oxazolone-induced dermatitis, leading to substantial reductions in ear edema/thickness, pro-inflammatory cytokines, and MPO activity. These effects were reversed by mifepristone, a steroid antagonist and confirmed by immunohistochemical and histopathological analysis. The data suggest that physalin E may be a potent and topically effective anti-inflammatory agent useful to treat the acute and chronic skin inflammatory conditions.
Asunto(s)
Antiinflamatorios/uso terapéutico , Dermatitis por Contacto/tratamiento farmacológico , Physalis/química , Secoesteroides/uso terapéutico , Animales , Inmunohistoquímica , Masculino , Ratones , Oxazolona/toxicidad , Acetato de Tetradecanoilforbol/toxicidadRESUMEN
BACKGROUND AND PURPOSE: Oncocalyxone A (OncoA) has a concentration-dependent anti-platelet activity. The present study aimed to further understand the mechanisms related to this effect. EXPERIMENTAL APPROACH: Human platelet aggregation was measured by means of a turbidimetric method. OncoA (32-256 microM) was tested against several platelet-aggregating agents, such as adenosine diphosphate (ADP), collagen, arachidonic acid (AA), ristocetin and thrombin. KEY RESULTS: OncoA completely inhibited platelet aggregation with a calculated mean inhibitory concentration (IC50-microM) of 122 for ADP, 161 for collagen, 159 for AA, 169 for ristocetin and 85 for thrombin. The anti-aggregatory activity of OncoA was not inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). OncoA, at a concentration that caused no significant anti-aggregatory activity, potentiated sodium nitroprusside (SNP) anti-aggregatory activity (18.8+/-2.9%-SNP vs 85.0+/-8.2%-SNP+OncoA). The levels of nitric oxide (NO) or cAMP were not altered by OncoA while cGMP levels were increased more than 10-fold by OncoA in resting or ADP-activated platelets. Flow cytometry revealed that OncoA does not interact with receptors for fibrinogen, collagen or P-selectin. Nevertheless, OncoA decreased the binding of antibodies to GP Ibalpha, a glycoprotein that is related both to von Willebrand factor and to thrombin-induced platelet aggregation. CONCLUSION AND IMPLICATIONS: OncoA showed anti-aggregatory activity in platelets that was associated with increased cGMP levels, not dependent on NO and with blocking GP Ibalpha glycoprotein. This new mechanism has the prospect of leading to new anti-thrombotic drugs.
Asunto(s)
Antraquinonas/farmacología , AMP Cíclico/biosíntesis , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Complejo GPIb-IX de Glicoproteína Plaquetaria/metabolismo , Adenosina Difosfato/farmacología , Adenosina Trifosfato/metabolismo , Adolescente , Adulto , Antraquinonas/aislamiento & purificación , Antraquinonas/metabolismo , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , AMP Cíclico/sangre , GMP Cíclico/sangre , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/sangre , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/metabolismo , Femenino , Citometría de Flujo , Guanilato Ciclasa/sangre , Guanilato Ciclasa/metabolismo , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Inhibidores de Agregación Plaquetaria/metabolismo , Unión Proteica , Tromboxano A2/fisiologíaRESUMEN
The essential oil of fresh leaves of Lippia aff. gracillis was analyzed by GC/MS and evaluated for its antibacterial effects. The results showed a moderate antibacterial activity and confirm the traditional uses of L. aff. gracillis.
Asunto(s)
Antibacterianos/farmacología , Lippia/química , Aceites Volátiles/farmacología , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/análisis , Hojas de la Planta/química , Staphylococcus aureus/efectos de los fármacosRESUMEN
A atividade larvicida de quatro saponinas monodesmosídicas (1-4) isoladas de Pentaclethra macroloba e de uma saponina bidesmosídica (5) isolada de Cordia piauhiensis foi avaliada sobre larvas de estágio 3 de Aedes aegypti. As larvas foram expostas a várias concentrações (500, 250, 100, 50, 25 e 12,5 mg/mL) das saponinas por um período de 24 h. Os resultados indicam que somente as saponinas 1-3 mostraram alta atividade larvicida, com CL50 variando de 18,6 a 27,9 mg/mL. Estes resultados ressaltam as potencialidades destas saponinas como possíveis agentes larvicidas naturais.
The larvicidal activity of the four monodesmoside saponins (1-4) isolated from Pentaclethra macroloba and one bidesmoside saponin (5) from Cordia piauhiensis was evaluated on 3rd instar larvae of Aedes aegypti. The larvae were exposed to serial concentrations (500, 250, 100, 50, 25 and 12.5 mg/mL) saponins for a period of 24 h. The results indicate that, only the saponins 1-3 showed high larvicidal activity, with LC50 ranging of 18,6-27,9 mg/mL. These results suggest that these can be used as natural larvicidal agents.
RESUMEN
No período de janeiro à dezembro de 2003 foram enviados ao Laboratório Central do estado do Ceará ( LACEN-Ce), 1.028 espécimes clínicos (urina), coletados de 112 pacientes com suspeita de tuberculose urogenital, onde 79 (7,7) destes espécimes apresentaram baciloscopia e cultura positiva para o complexo Mycobacterium tuberculosis. Dos 112 pacientes apenas 40 (35,7)...
Asunto(s)
Masculino , Femenino , Humanos , Tuberculosis Urogenital , Técnicas de Laboratorio Clínico , Mycobacterium tuberculosisRESUMEN
The present study evaluated the cytotoxic activity of nepetin and quercetin-3-O-glucoside, compounds isolated from the aerial parts of Eupatorium ballotaefolium. The antimitotic activity was determined as the ability to inhibit sea urchin eggs development and five tumor cells lines growth. Moreover, the activities of these compounds were compared to quercetin in the same models. Nepetin inhibited the proliferation of the five tumor cell lines, once quercetin-3-O-glucoside did not present any activity even at the highest tested concentration and quercetin only inhibited proliferation of the B16 cell line. On the sea urchin assay, nepetin and quercetin induced a dose-dependent inhibition on egg development, while quercetin-3-O-glucoside did not modify normalegg cleavage, even at the highest tested concentration (100 microg/ml).
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Eupatorium/química , Flavonoides/farmacología , Quercetina/análogos & derivados , Quercetina/farmacología , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Flavonas , Humanos , Erizos de MarRESUMEN
Auxemma oncocalyx Taub. belongs to the Boraginaceae family and is native to the Brazilian northeast where it is known as "pau-branco". We investigated the ability of the water soluble fraction isolated from the heartwood of A. oncocalyx to inhibit sea urchin egg development. This fraction contains about 80% oncocalyxone A (quinone fraction), a compound known to possess strong cytotoxic and antitumor activities. In fact, the quinone fraction inhibited cleavage in a dose-dependent manner [IC50 of 18.4 (12.4-27.2) microg/ml, N = 6], and destroyed the embryos in the blastula stage [IC50 of 16.2 (13.7-19.2) microg/ml, N = 6]. We suggest that this activity is due to the presence of oncocalyxone A. In fact, these quinones present in A. oncocalyx extract have strong toxicity related to their antimitotic activity.
Asunto(s)
Antraquinonas/toxicidad , Boraginaceae/química , Óvulo/efectos de los fármacos , Quinonas/toxicidad , Animales , Antraquinonas/aislamiento & purificación , Antineoplásicos/toxicidad , Daño del ADN , Extractos Vegetales/toxicidad , Quinonas/aislamiento & purificación , Erizos de MarRESUMEN
Auxemma oncocalyx Taub. belongs to the Boraginaceae family and is native to the Brazilian northeast where it is known as "pau-branco". We investigated the ability of the water soluble fraction isolated from the heartwood of A. oncocalyx to inhibit sea urchin egg development. This fraction contains about 80 percent oncocalyxone A (quinone fraction), a compound known to possess strong cytotoxic and antitumor activities. In fact, the quinone fraction inhibited cleavage in a dose-dependent manner [IC50 of 18.4 (12.4-27.2) æg/ml, N = 6], and destroyed the embryos in the blastula stage [IC50 of 16.2 (13.7-19.2) æg/ml, N = 6]. We suggest that this activity is due to the presence of oncocalyxone A. In fact, these quinones present in A. oncocalyx extract have strong toxicity related to their antimitotic activity
Asunto(s)
Animales , Antraquinonas , Boraginaceae , Óvulo , Extractos Vegetales , Quinonas , Antraquinonas , Antineoplásicos , Daño del ADN , Quinonas , Erizos de MarRESUMEN
Eleven known compounds and a new prenylated naphthoquinone, lippsidoquinone (13), were isolated from ethanol extracts of Lippia sidoides. Their structures were established by a combination of 1D and 2D NMR, IR, and EIMS spectral data analysis. The cytotoxic properties of compounds 3--13 were evaluated against HL60, SW1573, and CEM cell lines. Only tectol (6) and lippsidoquinone (13) exhibited significant activity against human leukemia cell lines HL60 and CEM.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Naftoquinonas/química , Naftoquinonas/farmacología , Plantas Medicinales/química , Aedes , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Biomphalaria , Brasil , Ensayos de Selección de Medicamentos Antitumorales , Insecticidas/química , Insecticidas/aislamiento & purificación , Insecticidas/toxicidad , Espectroscopía de Resonancia Magnética , Moluscocidas/química , Moluscocidas/aislamiento & purificación , Moluscocidas/toxicidad , Espectrofotometría Infrarroja , Células Tumorales CultivadasRESUMEN
Three anthracene derivatives, auxenone, oncocalyxonol and auxemim, were isolated from Auxemma ontocalyx. The structures of these compounds as 1,4,8-trihydroxy-2-methoxy-5-methyl-9,10-anthraquinone, rel-9alpha,11alpha-epoxy-1,4,8alpha,11alpha-tetrahydroxy-2-methoxy-8a beta-methyl-5,6,7,8,8a,9, 10,10a beta-octahydro-10-anthracenone and rel-8alpha,11beta-epoxy-2,11-dimethoxy-8a beta-methyl-5,6,7,8,8a,9-hexahydro-1,4-anthracenedione were determined by analysis of spectral data (1D and 2D NMR, IR, HREIMS and UV).
Asunto(s)
Antracenos/aislamiento & purificación , Magnoliopsida/química , Antracenos/química , Estructura Molecular , Análisis EspectralRESUMEN
The present work explored the anti-platelet effect produced by the quinone fractions (17.8, 35.7 and 71.4 microg/ml) isolated from the heartwood of Auxemma oncocalyx Taub. Our results show that the quinone fraction (QF) is a reversible and concentration-dependent inhibitor of human platelet aggregation induced by ADP, arachidonic acid (AA), collagen and thrombin. Besides, the QF effect was significantly potentiated after its association with aspirin or imidazole, and in this case, the AA-induced platelet aggregation was completely blocked. The addition of QF to L-arginine caused a small but significant increase in the percentage of platelet inhibition (13%) only when compared to QF alone. Finally, the addition of QF to pentoxifylline, a known phosphodiesterase inhibitor, resulted in significant potentiation (43% inhibition) of the antiplatelet effects seen with QF (9.7%) or PTX (10%) alone. Although QF presented an antiplatelet effect, it caused a significant decrease in bleeding time, manifested 3 h after oral (100 or 200 mg/Kg) or 1 and 3 h after intraperitonial (30 mg/Kg) administration. In conclusion. QF possibly acts through a combined cyclo-oxygenase and TxA2 synthase inhibition. Besides, QF also increases platelets cAMP levels which also contributes to its anti-aggregatory effects.