RESUMEN
Sweetness signals the nutritional value of food and may moreover be accompanied by a sensory suppression that leads to higher pain tolerance. This effect is well documented in infant rats and humans. However, it is still debated whether sensory suppression is also present in adult humans. Thus, we investigated the effects of sweet taste on the perception of the painful trigeminal stimulus capsaicin in two groups of healthy adult human subjects. A solution of 100 µM capsaicin was applied to the tip of the subject's tongues in order to stimulate trigeminal Aδ- and C-fiber nociceptors. When swallowed, 1M sucrose reduced the capsaicin-induced burning sensation by 29% (p ≤ 0.05) whereas a solution of similar taste intensity containing 1 µM quinine did not. Similarly, sucrose application to the frontal hemitongue suppressed the perception of the burning sensation induced by contralaterally applied capsaicin by 25% (p ≤ 0.01). We furthermore investigated the effects of documented unilateral transection of the chorda tympani nerve on capsaicin perception. In accordance with the ipsi-to-contralateral effect of sucrose on capsaicin perception in healthy subjects, hemiageusic subjects were more sensitive for capsaicin on the tongue contralateral to the taste nerve lesion (+38%; p ≤ 0.01). Taken together, these results argue I) for the existence of food intake-induced sensory suppression, if not analgesia, in adult humans and II) a centrally mediated suppression of trigeminal sensation by taste inputs that III) becomes disinhibited upon peripheral taste nerve lesion.
Asunto(s)
Capsaicina/farmacología , Nervio de la Cuerda del Tímpano/fisiología , Percepción del Dolor/efectos de los fármacos , Fármacos del Sistema Sensorial/farmacología , Gusto/fisiología , Lengua/inervación , Adulto , Anciano , Nervio de la Cuerda del Tímpano/lesiones , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Sacarosa/administración & dosificación , Edulcorantes/farmacología , Gusto/efectos de los fármacos , Lengua/efectos de los fármacos , Adulto JovenRESUMEN
Two new prenylated flavanones, 2 S-3'-(2-hydroxy-3-methylbut-3-enyl)licoflavone-4'-methyl ether ( 3) and 2 S-3'-(2-hydroxy-3-methylbut-3-enyl)abyssinone II ( 4), and four known flavanones ( 1, 2, 5, 6) were isolated from the stem bark of Erythrina addisoniae. The structures were elucidated on the basis of their spectroscopic and physicochemical data. None of the compounds showed antioxidative properties. 4'-Methylabyssinone V ( 1) and abyssinoflavanone VII ( 6) showed moderate cytotoxic activity (IC 50 = 5 and 3.5 micromol/L, respectively), but apoptosis (caspase-3/7-activation, nuclear fragmentation) was selectively induced by abyssinoflavanone VII ( 6).
Asunto(s)
Apoptosis/efectos de los fármacos , Erythrina/química , Flavanonas/aislamiento & purificación , Animales , Flavanonas/química , Flavanonas/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Corteza de la Planta/química , RatasRESUMEN
The genus Erythrina (Leguminosae), consisting of over 100 different species, is distributed in tropical regions. In traditional medicine, Erythrina species are used to treat cancer, but little is known about the anticancer mechanisms. From the stem bark of Erythrina addisoniae Hutch. & Dalziel, six prenylated pterocarpans were isolated and analysed for pharmacological activity: While calopocarpin, cristacarpin, orientanol c, and isoneorautenol showed only a weak or moderate toxicity in H4IIE hepatoma cells (EC(50)-value> 25 microM), the toxicity of neorautenol and phaseollin was in the low micromolar range (EC(50)-value: 1 and 1.5 microM, respectively). We further focused on these two substances showing that both increased caspase 3/7 activity and nuclear fragmentation as markers for apoptotic cell death. Neorautenol (10 microM, 2h), but not phaseollin induced the formation of DNA strand breaks (comet assay). Both substances showed no effect on NF-kappaB signalling (SEAP assay: basal activity and stimulation with TNF-alpha), on the other hand both pterocarpans (10 microM, 2 h) decreased the activation of the ERK kinase (p44/p42), an mitogen activated protein kinase which is associated with cell proliferation. We conclude that the pterocarpans phaseollin and neorautenol may be responsible for the anticarcinogenic actions of the plant extract reported in the literature. Further analysis of these substances may lead to new pharmacons to be used in cancer therapy.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Erythrina , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Isoflavonas/farmacología , Extractos Vegetales/farmacología , Pterocarpanos/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Roturas del ADN de Cadena Simple , Relación Dosis-Respuesta a Droga , Activación Enzimática , Erythrina/química , Concentración 50 Inhibidora , Isoflavonas/aislamiento & purificación , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , FN-kappa B/metabolismo , Necrosis , Fosforilación , Corteza de la Planta , Extractos Vegetales/aislamiento & purificación , Prenilación , Pterocarpanos/aislamiento & purificación , Pterocarpanos/toxicidad , RatasRESUMEN
The indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of beta-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg(-1) day(-1) ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (DeltaT(m) value) or toxicity in the mouse-malaria model.
Asunto(s)
Alcaloides/química , Alcaloides/síntesis química , Antimaláricos/síntesis química , Indoles , Quinolinas , Alcaloides/farmacología , Animales , Antimaláricos/química , Antimaláricos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Bovinos , ADN/química , Ensayos de Selección de Medicamentos Antitumorales , Calefacción , Hemina/química , Alcaloides Indólicos , Malaria/tratamiento farmacológico , Ratones , Desnaturalización de Ácido Nucleico , Plasmodium berghei , Plasmodium falciparum/efectos de los fármacos , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Fourteen Ghanaian plants used in folk medicine to treat fever/malaria were screened for activity against Plasmodium falciparum (strain K1) and were tested for general toxicity to the brine shrimp. Extracts from three of the plants, Pleiocarpa mutica, Cleistopholis patens and Uvaria chamae were found to have significant antiplasmodial activity. The extract of U. chamae was toxic to brine shrimps. These findings lend support to the use of these plants in traditional medicine. Possible toxicity due to U. chamae is a cause for concern. Five known alkaloids, pleiocarpine (1), kopsinine (2), pleiocarpamine (3), eburnamine (4) and pleiomutinine (5) were isolated from the roots of P. mutica. This is the first report of the occurrence of (4) in P. mutica. Compound (5) was the most active against P. falciparum (IC50 = 5 microM). Although (1) was inactive against malaria parasites in vitro, it was moderately active against P. berghei in mice (25 mg kg(-1) daily for 4 days reduced parasitaemia by 28.5% compared to untreated controls).