RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Heinsia crinita is used in traditional medicine for the treatment of febrile illness and erectile dysfunction. Its stem bark powder is found in some peripheral markets in the Democratic Republic of the Congo (DRC) as a remedy against malaria. Investigations were conducted on crude extracts of leaves, fruits and stem barks in view to validate their use and to determine which plant part possesses the best antiplasmodial properties. MATERIALS AND METHODS: Different plant parts were extracted with methanol, ethanol and dichloromethane. Based on the preliminary assays, the dichloromethane extract of the stem bark was subjected to fractionation using preparative HPLC system and column chromatography. This step led to the isolation of two new iridoids which had their structures elucidated by NMR, UV, MS and FT-IR spectroscopic techniques. Extracts and pure compounds were tested in vitro against the 3D7 strain of Plasmodium falciparum. The inhibition of the parasite growth was evaluated in vitro by colorimetric method (p-LDH assay) and their cytotoxicity evaluated in vitro against the human non-cancer fibroblast cell line (WI38) through WST1 assay. The in vivo antiplasmodial activity was assessed by the inhibition of Plasmodium berghei growth in infected mice treated with the ethanol extract of H. crinita stem bark at the concentrations of 200 and 300mg/Kg/day per os, using a protocol based on the 4-d suppressive test of Peters and compared to a non-treated negative control group of mice (growth =100%). Finally the antioxidant activity of the same extract was evaluated using ABTS, DPPH and cell-based assays. RESULTS: A moderate in vitro antiplasmodial activity was observed for the dichloromethane extract of the stem bark of H. crinita (IC50 =29.2±1.39µg/mL) and for the two new iridoids, lamalbide 6, 7, 8- triacetate (IC50 =16.39±0.43µg/mL) as well as for its aglycone lamiridosin 6, 7, 8-triacetate (IC50 =0.44.56±1.12µg/mL). The ethanolic stem bark extract (200 and 300mg/kg/day, oral route) showed a moderate in vivo antimalarial activity in Plasmodium berghei-infected mice with 27.84±2.75% and 48.54±3.76% of inhibition of the parasite growth, respectively (p<0.01).). This extract displayed high cellular antioxidant activity using dichlorofluorescein-diacetate (DCFDA) on HL-60 monocytes. These crude extracts and pure compounds tested at the higher concentration of 100µg/mL did not show any cytotoxicity against WI38 cells. CONCLUSIONS: The results showed that H. crinita extracts possess antimalarial activity and contain some unusual iridoids with moderate antiplasmodial activity, therefore justifying to some extent its traditional use by the local population in DRC for this purpose. This is the first report of the isolation and antiplasmodial activity of these two new iridoids.

Asunto(s)

Antimaláricos , Iridoides , Malaria/tratamiento farmacológico , Extractos Vegetales , Rubiaceae , Animales , Antimaláricos/análisis , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Línea Celular , Supervivencia Celular/efectos de los fármacos , Femenino , Frutas , Células HL-60 , Humanos , Iridoides/análisis , Iridoides/farmacología , Iridoides/uso terapéutico , Malaria/parasitología , Ratones , Corteza de la Planta , Extractos Vegetales/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Plasmodium berghei/efectos de los fármacos , Plasmodium berghei/crecimiento & desarrollo , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/crecimiento & desarrollo , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

African populations use traditional medicines in their initial attempt to treat a range of diseases. Nevertheless, accurate knowledge of the composition of these drugs remains a challenge in terms of ensuring the health of population and in order to advance towards improved traditional medicines (ITMs). In this paper chromatographic methods were developed for qualitative and quantitative analyses of a per os antimalarial ITM containing Garcinia kola. The identified analytical markers were used to establish TLC and HPLC fingerprints. G. kola seeds were analysed by HPLC to confirm the identity of the extract used by the Congolese manufacturer in the ITM. The main compounds (GB1, GB2, GB-1a and Kolaflavanone) were isolated by preparative TLC and identified by UPLC-MS and NMR. For the quantification of the major compound GB1, a simple and rapid experimental design was applied to develop an LC method, and then its validation was demonstrated using the total error strategy with the accuracy profile as a decision tool. The accurate results were observed within 0.14-0.45mg/mL range of GB1 expressed as naringenin. The extracts used in several batches of the analysed oral solutions contained GB1 (expressed as naringenin) within 2.04-2.43%. Both the fingerprints and the validated LC-DAD were found suitable for the quality control of G. kola-based raw material and finished products, respectively.

Asunto(s)

Antimaláricos/análisis , Biflavonoides/análisis , Cromatografía Líquida de Alta Presión/métodos , Garcinia kola/química , Extractos Vegetales/química , Antimaláricos/aislamiento & purificación , Biflavonoides/aislamiento & purificación , Flavanonas/análisis , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Semillas/química

RESUMEN

This study aimed to determine the rotenoid content of leaf extracts of the white (TVW) and purple (TVP) varieties of Tephrosia vogelii, both collected in North-Kivu Province, Democratic Republic of Congo and to evaluate their in vitro acaricidal efficacy on the tick Rhipicephalus appendiculatus. The high performance liquid chromatography analysis of rotenoid compounds from those extracts revealed that the contents of rotenone and deguelin were respectively higher in the leaves of TVW (0.044% and 1.13%) than in TVP (0.014% and 0.66%). Batches of 20 live adult ticks were immersed for 15 min in six different doses of each plant extract (0.625; 1.25; 2.5; 5; 10 and 20mg/mL of distilled water) and in the solution of Milbitraz(®) (12.5%m/v emulsifiable concentrate of amitraz) as a positive control. Additionally 9.5% ethanol and distilled water control groups were included. Tick mortalities were recorded every 24h for 5 days. The results indicated that there was no significant difference (P>0.05) between the acaricidal effect of Milbitraz(®) and the plant material used at a dose of at least 2.5 or 5mg/mL for TVW and TVP respectively. However, the dose response relationship determined at the fifth day after treatment showed a similar acaricidal effect for the two plant varieties with similar lethal dose 50 (LD(50)) of 0.83 and 0.81 mg/mL for TVW and TVP respectively. It is concluded that T. vogelii leaves may be used for the control of R. appendiculatus in areas where synthetic acaricides are either not available or affordable. However, T. vogelii extract should be sprayed in order to limit the potential risks of ecotoxicity linked to rotenoid compounds.

Asunto(s)

Acaricidas/farmacología , Extractos Vegetales/farmacología , Rhipicephalus/efectos de los fármacos , Rotenona/farmacología , Tephrosia/química , Acaricidas/química , Acaricidas/aislamiento & purificación , Animales , República Democrática del Congo , Relación Dosis-Respuesta a Droga , Dosificación Letal Mediana , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Rotenona/análogos & derivados , Rotenona/química , Rotenona/aislamiento & purificación

RESUMEN

The HPLC separation of six alkaloids extracted from Strychnos usambarensis leaves has been developed and optimized by means of a powerful methodology for modelling chromatographic responses, based on three steps, i.e. design of experiments (DoE), independent component analysis (ICA) and design space (DS). This study was the first application of a new optimization strategy to a complex natural matrix. The compounds separated are the isomers isostrychnopentamine and strychnopentamine, 10-hydroxyusambarine and 11-hydroxyusambarine, also strychnophylline and strychnofoline. Three LC parameters have been optimized using a multifactorial design comprising 29 experiments that includes 2 center point replicates. The parameters were the percentage of organic modifiers used at the beginning of a gradient profile which consisted in different proportions of methanol (MeOH) and acetonitrile (MeCN), the gradient time to reach 70% of organic modifiers starting from the initial percentage and the percentage of MeCN found in the mobile phase. Subsequent to the experimental design application, predictive multilinear models were developed and used in order to provide optimal analytical conditions. The optimum assay conditions were: methanol/acetonitrile-sodium pentane sulfonate (pH 2.2; 7.5 mM) (33.4:66.6, v/v) at a mobile phase flow rate of 1 ml/min during a 40.6 min gradient time. The initial organic phase contained 3.7% MeCN and 96.3% MeOH. The method showed good agreement between the experimental data and predictive value throughout the studied parameters space. Improvement of the analysis time and optimized separation for the compounds of interest was possible due to the original and powerful tools applied. Finally, this study permitted the acquisition of isomers profiles allowing the identification of the optimal collecting period of S. usambarensis.

Asunto(s)

Alcaloides/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Extractos Vegetales/aislamiento & purificación , Proyectos de Investigación , Strychnos/química , Alcaloides/química , Bioestadística , Cromatografía Líquida de Alta Presión/estadística & datos numéricos , Estructura Molecular , Extractos Vegetales/química , Hojas de la Planta/química , Proyectos de Investigación/estadística & datos numéricos

RESUMEN

AIM OF THE STUDY: Antiplasmodial activity, inhibition of nitric oxide (NO) overproduction, and anti-proliferative activity were investigated in vitro to evaluate the bioactive potential of the traditional pharmacopoeia of the Mascarene Archipelago, which is known for its biodiversity and for the richness of its endemic flora. MATERIALS AND METHODS: A total of 45 methanol (MeOH) and dichloromethane (DCM) extracts were prepared from 19 plant species collected on Réunion and Mauritius Islands. Ninety-six-well microplate assays were performed on chloroquine sensitive Plasmodium falciparum 3D7 strain, on LPS-stimulated Raw 264.7 murine macrophages and on A-549, DLD-1 and WS1 human cells. Activity was evaluated through spectrophotometric methods. RESULTS: Activity was attributed to plant extracts expressing IC(50)<50µg/ml for antiplasmodial response, IC(50)<100µg/ml for cytotoxicity, and IC(50)<130µg/ml for anti-inflammatory reaction. The majority of the extracts tested (69%) exhibited potency in at least one of these three types of activity. This is the first report describing promising antiplasmodial activity (IC(50)<15µg/ml) for Psiadia dentata DCM extract and Terminalia bentzoe MeOH bark extract. NO inhibition assay revealed seven interesting plants, described for the first time as anti-inflammatory: Aphloia theiformis, Buddleja salviifolia, Eupatorium riparium, Hiptage benghalensis, Psiadia arguta, Psiadia dentata, and Scutia commersonii. Finally, anti-proliferative activity was observed for two endemic species, Geniostoma borbonicum and Nuxia verticillata. CONCLUSION: Using the criterion of endemism as part of the criteria for traditional medicinal use raises the chances of finding original active principles. In our case, 86% of the endemic plants tested displayed pharmacological interest.

Asunto(s)

Antiinflamatorios/uso terapéutico , Antimaláricos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Inflamación/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Plasmodium falciparum/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Islas del Oceano Índico , Inflamación/inducido químicamente , Concentración 50 Inhibidora , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Medicina Tradicional , Ratones , Óxido Nítrico/antagonistas & inhibidores , Extractos Vegetales/farmacología

RESUMEN

AIM OF THE STUDY: The aim of this study was to evaluate the antiplasmodial properties of 13 plants used against malaria in traditional medicine in Burkina Faso. MATERIALS AND METHODS: In vitro antiplasmodial activity of dichloromethane, methanol and aqueous crude extracts obtained from vegetal samples collected in Burkina Faso was first evaluated on the Plasmodium falciparum 3D7 chloroquine-sensitive strain using a colorimetric method. RESULTS: Thirteen extracts obtained from 8 different species were found to exhibit antiplasmodial activity (IC(50)<50 microg/ml). Five species demonstrated a moderate activity (15 microg/ml

Asunto(s)

Extractos Vegetales/farmacología , Plantas Medicinales/química , Plasmodium falciparum/efectos de los fármacos , Animales , Burkina Faso , Especificidad de la Especie

RESUMEN

AIM OF THE STUDY: The in vitro antiplasmodial activity and cytotoxicity of methanolic and dichloromethane extracts from five Congolese plants were evaluated. The plants were selected following an ethnobotanical survey conducted in D.R. Congo and focusing on plants used traditionally to treat malaria. The in vivo antimalarial activity of aqueous and methanolic extracts active in vitro was also determined in mice infected by Plasmodium berghei berghei. MATERIALS AND METHODS: The growth inhibition of Plasmodium falciparum strains was evaluated using the measurement of lactate dehydrogenase activity. The extracts (aqueous, CH(3)OH, EtOH and CH(2)Cl(2)) were prepared by maceration and tested in vitro against the 3D7 (chloroquine sensitive) and W2 (chloroquine resistant) strains of Plasmodium falciparum and against the human normal fetal lung fibroblasts WI-38 to determine the selectivity index. Some extracts were also used at the dose of 300 mg/kg to evaluate their activity in mice infected since 4 days by Plasmodium berghei. RESULTS: Two plants presented a very high activity (IC(50)<3 microg/ml). These plants were Strychnos icaja roots bark (MeOH and CH(2)Cl(2)) and Physalis angulata leaves (MeOH and CH(2)Cl(2)). One plant (Anisopappus chinensis whole plant, MeOH and CH(2)Cl(2)) presented a high activity (IC50<15 microg/ml). The extracts of Anisopappus chinensis and Physalis angulata showed also a good inhibition of parasitemia in vivo. Flavonoids, phenolic acids and terpenes were identified in these plants by a general phytochemical screening method. CONCLUSION: Three plants showed a very interesting antiplasmodial activity (Anisopappus chinensis, Physalis angulata and Strychnos icaja) and one of them showed a good selectivity index (>10, Anisopappus chinensis). Anisopappus chinensis and Physalis angulata were also active in vivo.

Asunto(s)

Antimaláricos/farmacología , Malaria/tratamiento farmacológico , Medicinas Tradicionales Africanas , Extractos Vegetales/farmacología , Plantas Medicinales/química , Animales , Antimaláricos/efectos adversos , Antimaláricos/aislamiento & purificación , Técnicas de Cultivo de Célula , Línea Celular , Supervivencia Celular/efectos de los fármacos , República Democrática del Congo , Modelos Animales de Enfermedad , Fibroblastos/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Malaria/microbiología , Ratones , Ratones Endogámicos , Extractos Vegetales/efectos adversos , Extractos Vegetales/aislamiento & purificación , Plasmodium berghei/efectos de los fármacos , Plasmodium berghei/patogenicidad , Plasmodium falciparum/efectos de los fármacos

RESUMEN

AIM OF THE STUDY: In our study, methanol, dichloromethane and aqueous extracts of 13 Rwandan medicinal plants used in the treatment of malaria were tested for in vitro antiplasmodial activity. MATERIALS AND METHODS: The growth inhibition of chloroquine-sensitive Plasmodium falciparum strain (3D7) was evaluated using the measurement of lactate dehydrogenase activity. The active extracts were also tested against the chloroquine-resistant Plasmodium falciparum strain (W2) and for cytotoxicity assay using human normal foetal lung fibroblasts (WI-38). RESULTS: The majority of the plants tested showed an antiplasmodial activity and the best results were observed with dichloromethane leaf and flower extracts of Tithonia diversifolia, leaf extract of Microglossa pyrifolia and root extract of Rumex abyssinicus, methanol leaf extract of Fuerstia africana, root bark extracts of Zanthoxylum chalybeum and methanol bark extract of Terminalia mollis. Those extracts were active (IC(50)<15mug/ml) on both chloroquine-sensitive and resistant strains of Plasmodium falciparum. Zanthoxylum chalybeum, Solanecio mannii and Terminalia mollis presented the best selectivity index. CONCLUSIONS: The traditional use of most of the plant evaluated was confirmed by the antiplasmodial test. This study revealed for the first time the antiplasmodial activity of two plants: Terminalia mollis and Rumex abyssinicus.

Asunto(s)

Antimaláricos/uso terapéutico , Antineoplásicos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Antimaláricos/farmacología , Antineoplásicos/farmacología , Línea Celular , Humanos , Extractos Vegetales/farmacología , Plasmodium falciparum/efectos de los fármacos , Rwanda

RESUMEN

Fagara zanthoxyloides Lam. (syn. Zanthoxylum zanthoxyloides) (Rutaceae) is the most cited Fagara species for the treatment and the prevention of sickle cell disease crisis. Sickle cell anemia (SCA) is a public health problem in many countries particularly in Africa. The present study was designed to evaluate the antisickling properties of three isomeric divanilloylquinic acids (3,4-O-divanilloylquinic acid or burkinabin A; 3,5-O-divanilloylquinic acid or burkinabin B and 4,5-O-divanilloylquinic acid or burkinabin C) identified previously by LC/MS/NMR analysis in the root bark of F. zanthoxyloides [Ouattara et al., 2004. LC/MS/NMR analysis of isomeric divanilloylquinic acids from the root bark of Fagara zanthoxyloides Lam. Phytochemistry 65, 1145-1151]. The three isomers showed interesting antisickling properties which increased from burkinabins A to C.

Asunto(s)

Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Ácido Quínico/análogos & derivados , Ácido Vanílico/análogos & derivados , Zanthoxylum , África , Cromolin Sódico/uso terapéutico , Humanos , Isomerismo , Corteza de la Planta , Raíces de Plantas , Ácido Quínico/aislamiento & purificación , Ácido Quínico/uso terapéutico , Ácido Vanílico/aislamiento & purificación , Ácido Vanílico/uso terapéutico , Zanthoxylum/química

RESUMEN

AIM OF THE STUDY: Nine plants from Reunion Island, selected using ethnopharmacology and chemotaxonomy, were investigated for their potential antimalarial value. MATERIALS AND METHODS: Thirty-eight extracts were prepared by maceration using CH(2)Cl(2) and MeOH, and were tested for in vitro activity against the 3D7 and W2 strain of Plasmodium falciparum. The most active extracts were then tested for in vitro cytotoxicity on human WI-38 fibroblasts to determine the selectivity index. Those extracts were also investigated in vivo against Plasmodium berghei infected mice. RESULTS: Most active of the extracts tested were the dichloromethane leaves extracts of Nuxia verticillata Lam. (Buddlejaceae), Psiadia arguta Voigt. (Asteraceae), Lantana camara L. (Verbenaceae), the methanol extracts from Aphloia theiformis (Vahl) Benn. (Aphloiaceae) bark, and Terminalia bentzoe L. (Combretaceae) leaves displaying in vitro IC(50) values ranging from 5.7 to 14.1mug/ml. Extracts from Psiadia, Aphloia at 200mg/(kgday) and Teminalia at 50mg/(kgday) also exhibited significant (p<0.0005) parasite inhibition in mice: 75.5%, 65.6% and 83.5%, respectively. CONCLUSION: Two plants showed interesting antimalarial activity with good selectivity: Aphloia theiformis and Terminalia bentzoe. Nuxia verticillata still needs to be tested in vivo, with a new batch of plant material.

Asunto(s)

Antimaláricos/uso terapéutico , Malaria/tratamiento farmacológico , Fitoterapia , Plantas Medicinales/química , Plasmodium berghei/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/aislamiento & purificación , Antimaláricos/farmacología , Células Cultivadas , Cloroquina , Evaluación Preclínica de Medicamentos , Farmacorresistencia Microbiana , Femenino , Fibroblastos/efectos de los fármacos , Humanos , Magnoliopsida/química , Ratones , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Distribución Aleatoria , Reunión

RESUMEN

The antiplasmodial and antitrypanosomal activities of Triclisia sacleuxii (Pierre) Diels were investigated on three Plasmodium falciparum strains [FcB1, 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) strains] and on Trypanosoma brucei Tbsf 221. Roots, stems and leaves ethanolic extracts as well as crude tertiary and quaternary alkaloids fractions were considered. Whereas the ethanolic extracts and quaternary crude alkaloids fractions exhibited no significant activity, the roots and stems tertiary alkaloid fractions revealed interesting growth inhibition against the Plasmodium FcB1 and Trypanosoma Tbsf 221 strains. The IC(50) were 1.04 and 0.89 microg/ml for roots, 2.50 and 0.91 microg/ml for stems. The leaves tertiary alkaloids fraction also showed a promising antitrypanosomal activity (IC(50): 1.85 microg/ml). Phytochemical analysis of the roots tertiary alkaloids fraction yielded four major compounds, phaeanthine, N-methylapateline, 1,2-dehydroapateline and 1,2-dehydrotelobine, which were identified on the basis of their spectroscopic data. The four compounds displayed (in vitro) antitrypanosomal activity with IC(50) of 2.68, 1.19, 1.06 and 1.11 microM, respectively. They also demonstrated antiplasmodial activity on Plasmodium falciparum 3D7, with IC(50) of 1.72, 0.93, 1.39 and 12.4 microM respectively and on the chloroquine-resistant W2 with IC(50) of 0.35, 1.10, 1.63 and 1.52 microM.

Asunto(s)

Antimaláricos/farmacología , Menispermaceae/química , Extractos Vegetales/farmacología , Tripanocidas/farmacología , Animales , Etanol/química , Humanos , Técnicas In Vitro , Plasmodium falciparum/efectos de los fármacos , Trypanosoma brucei brucei/efectos de los fármacos

RESUMEN

The inclusion complexes of tagitinin C with beta-, 2,6-di-O-methyl-beta- and gamma-cyclodextrin (CyD) was investigated in aqueous medium. The stoichiometric ratios and stability constants (K(f)) which describe the extent of formation of the complexes have been determined by UV spectroscopy and direct current tast polarography (DC(tast)), respectively. For each complex, a 1:1 molar ratio was formed in solution and the trend of stability constants was K(f) (2,6-di-O-methyl-beta-CyD)>K(f) (gamma-CyD)>K(f) (beta-CyD). The effect of molecular encapsulation on the photochemical conversion of tagitinin C was evaluated. No significant protection efficacy was noticed with beta- and gamma-CyD for the complexed drug with the respect to the free one. On the other hand, the photochemical conversion rate was slowed in presence of 2,6-di-O-methyl-beta-CyD. Data from (1)H NMR and ROESY experiments provided a clear evidence of formation of inclusion complexes. The lactone, the ester and the unsaturated ketone parts of tagitinin C inserted into the wide rim of the CyDs torus. These experimental results were confirmed by the molecular modeling using semiempirical Austin Model 1 (AM1) method.

Asunto(s)

Ciclodextrinas/química , Sesquiterpenos/química , Fenómenos Químicos , Química Física , Composición de Medicamentos , Electroquímica , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Fotoquímica , Polarografía , Espectrofotometría Ultravioleta , Agua

RESUMEN

Magnistipula butayei subsp. montana (Chrysobalanaceae) is known, in the Great Lakes Region, to possess toxicological properties. In this paper, we investigated the acute toxicity (dose levels 50-1600 mg/kg) of its aqueous extract, administered orally to adult Wistar rats. This study demonstrated that the freeze-dried aqueous extract (5%, w/w) possesses high toxicity. The extract caused hypothermia, neurological disorders, including extensor reflex of maximal convulsive induced-seizures at about 2 h after the administered dose, and death occurred (LD50=370 mg/kg) in a dose dependent manner. Blood parameter evaluation revealed slight variations, but these might not have clinical relevance. Histological examination of internal organs (lungs, liver, heart and kidneys) did not reveal any abnormality in the treated group compared to the control. Therefore, it can be concluded that Magnistipula butayei subsp. montana aqueous extract, given orally, is toxic and that its target is the central nervous system. General phytochemical screening revealed that the plant did not contain significant amounts of products known to be toxic, such as alkaloids or cardioactive glycosides, but only catechic tannins, amino acids, saponins and other aphrogen principles in the three parts of the species (fruit, leave and bark).

Asunto(s)

Sistema Nervioso Central/efectos de los fármacos , Chrysobalanaceae/química , Extractos Vegetales/toxicidad , África Central , Animales , Antocianinas/aislamiento & purificación , Temperatura Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Frutas , Dosificación Letal Mediana , Masculino , Corteza de la Planta , Extractos Vegetales/química , Hojas de la Planta , Ratas , Ratas Wistar , Saponinas/aislamiento & purificación , Convulsiones/etiología , Taninos/aislamiento & purificación

RESUMEN

Further to a systematic chemotaxonomic study of Uzbek Haplophyllum A. Juss. plants selected on ethnopharmacological data, 14 alkaloids were screened for their cytotoxic properties. As a first selection for interesting compounds, each alkaloid was tested against two human cancer cell lines (HeLa and HCT-116), using WST-1 reagent. Of the 14 alkaloids, 5 were cytotoxic when tested against the HeLa line with an IC50 < 100 microM. These five compounds consisted of three furoquinolines: skimmianine; haplopine and gamma-fagarine and two pyranoquinolones: flindersine and haplamine. Only haplamine was active against the HCT-116 line. The cytotoxic properties of these five alkaloids were further investigated against five additional human cancer cell lines. Their structure-activity relationships will be discussed. Of these five pre-selected alkaloids, only haplamine showed significant cytotoxic activity against all the tested cell lines. This is the first report of the cytotoxic activity of haplamine. Finally, this pyranoquinolone alkaloid was tested here against 14 different cancer cell lines and against normal skin fibroblasts.

Asunto(s)

Alcaloides/farmacología , Antineoplásicos Fitogénicos/farmacología , Rutaceae/química , Alcaloides/química , Alcaloides/clasificación , Alcaloides/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/clasificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Humanos , Estructura Molecular

RESUMEN

Methanol and water extracts of the root of Epinetrum villosum (Exell) Troupin (Menispermaceae) were found to exhibit antimicrobial and antiplasmodial activities. Investigation of the active methanol fraction led to the isolation of four bisbenzylisoquinoline alkaloids, i.e., cycleanine, cycleanine N-oxide, isochondodendrine and cocsoline. Structures were established by spectroscopic methods. Cocsoline displayed antibacterial and antifungal activities (MIC values of 1000-15.62 and 31.25 microg/ml, respectively). Isochondodendrine was found to have the most potent antiplasmodial activity (IC50 = 0.10 microg/ml), whereas the IC50 on HCT-116 human colon carcinoma cells was 17.5 microg/ml (selectivity index 175). Cycleanine acted against HIV-2 (EC50=1.83 microg/ml) but was at least 10-fold less active against HIV-1. Cycleanine N-oxide showed no activity towards all tested microorganisms.

Asunto(s)

Alcaloides/farmacología , Antibacterianos/farmacología , Fármacos Anti-VIH/farmacología , Antifúngicos/farmacología , Antimaláricos/farmacología , Bencilisoquinolinas/farmacología , Menispermaceae , Extractos Vegetales/farmacología , Raíces de Plantas/química , Animales , Células HCT116 , Humanos , Pruebas de Sensibilidad Microbiana , Plasmodium falciparum/efectos de los fármacos

RESUMEN

Feeding stemmadenine to Catharanthus roseus cell suspension culture resulted in the accumulation of catharanthine, tabersonine and condylocarpine. Condylocarpine is not an intermediate in the pathway to catharanthine or tabersonine when it is fed to the cultures. The results support the hypothesis that stemmadenine is an intermediate in the pathway to catharanthine and tabersonine.

Asunto(s)

Alcaloides/biosíntesis , Catharanthus/metabolismo , Alcaloides Indólicos/farmacocinética , Células Cultivadas

RESUMEN

In vivo magnetic resonance imaging (MRI) and angiography were applied to the marine spider crab Maja squinado for a study of temperature effects and thermal tolerance. Ventilation and haemolymph circulation were investigated during progressive cooling from 12 degrees C to 2 degrees C. The anatomical resolution of MR images from Maja squinado obtained with a standard spin echo sequence were suitable to resolve the structures of various internal organs. The heart of the animal could be depicted without movement artifacts. The use of a flow compensated gradient echo sequence allowed simultaneous observations of ventilation, reflected by water flow through the gill chambers as well as of haemolymph flow. Simultaneous investigation of various arteries was possible by use of flow weighted MRI. In addition to those accessible by standard invasive flow sensitive doppler sensors, flow changes in gill, leg arteries and the venous return could be observed. Both ventilation and haemolymph flow decreased during progressive cooling and changes in haemolymph flow varied between arteries. Haemolymph flow through the Arteria sternalis, some gill and leg arteries was maintained at low temperatures indicating a reduced thermal sensitivity of flow in selected vessels. In support of previous invasive studies of haemolymph flow as well as heart and ventilation rates, the results demonstrate that the operation of gills and the maintenance of locomotor activity are critical for cold tolerance. A shift in haemolymph flow between arteries likely occurs to ensure the functioning of locomotion and ventilation in the cold.

Asunto(s)

Braquiuros/fisiología , Frío , Hemolinfa/fisiología , Angiografía por Resonancia Magnética , Ventilación Pulmonar/fisiología , Animales , Regulación de la Temperatura Corporal/fisiología

RESUMEN

Two new quaternary indole alkaloids 5',6'-dehydroguiachrysine (1) and 5',6'-dehydroguiaflavine (2) were isolated from Strychnos guianensis stem bark. Their structures were determined by analysis of spectral data. Their inhibitory effects on neuromuscular transmission are also reported and compared to that of other quaternary alkaloids.

Asunto(s)

Alcaloides/aislamiento & purificación , Indoles/aislamiento & purificación , Loganiaceae/química , Tallos de la Planta/química , Alcaloides/química , Indoles/química , Estructura Molecular , Análisis Espectral

RESUMEN

Eight naturally occurring monoindole alkaloids were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth and, in drug combination, to reverse the resistance of a chloroquine-resistant strain of Plasmodium falciparum. None of these indole alkaloids has significant intrinsic antiplasmodial activity (IC(50) > 10 microM or 5 microg/ml). Nevertheless, three alkaloids (icajine, isoretuline and strychnobrasiline) did reverse chloroquine resistance at concentrations between 2.5 and 25 microg/ml (IF of 12.82 for isoretuline on W2 strain). The Interaction Factor (IF) equals 2, < 2, or > 2 for additive, antagonistic or synergistic effects of alkaloids on chloroquine inhibition, respectively. Icajine and isoretuline were also assessed in vitro for their mefloquine potentiating activity on a mefloquine-resistant strain of Plasmodium falciparum. Only icajine proved to be synergistic with mefloquine (IF = 15.38).

Asunto(s)

Alcaloides/farmacología , Antimaláricos/farmacología , Cloroquina/farmacología , Indoles/farmacología , Mefloquina/farmacología , Plasmodium falciparum/efectos de los fármacos , Estricnina/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/toxicidad , Animales , Colon/citología , Resistencia a Múltiples Medicamentos , Sinergismo Farmacológico , Humanos , Indoles/química , Indoles/aislamiento & purificación , Indoles/toxicidad , Concentración 50 Inhibidora , Estructura Molecular , Plasmodium falciparum/crecimiento & desarrollo , Estricnina/análogos & derivados , Estricnina/química , Estricnina/aislamiento & purificación , Estricnina/toxicidad , Células Tumorales Cultivadas

RESUMEN

Excellent symptom management is paramount in palliative care. Without it, the individual patient will be unable to focus appropriately on other issues of concern, including those of a psychosocial, emotional, or spiritual nature. This article reviews current pharmacologic and nonpharmacologic interventions for symptoms commonly encountered in palliative care. These symptoms are organized into gastrointestinal, respiratory and neuropsychiatric categories.

Asunto(s)

Tos/prevención & control , Delirio/prevención & control , Disnea/prevención & control , Enfermedades Gastrointestinales/prevención & control , Trastornos del Humor/prevención & control , Cuidado Terminal/métodos , Tos/etiología , Delirio/etiología , Disnea/etiología , Familia/psicología , Enfermedades Gastrointestinales/etiología , Humanos , Trastornos del Humor/etiología , Educación del Paciente como Asunto , Rol del Médico , Calidad de Vida , Cuidado Terminal/psicología