RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Clausena lansium (Fool's Curry Leaf) is used for various ethnomedical conditions in some countries, including bronchitis, malaria, viral hepatitis, acute and chronic gastro-intestinal inflammation, and as a spicy substitute of the popular Curry leaf tree (Murraya koenigii). AIM OF THE STUDY: This study was to evaluate the ethnomedical uses of the stem bark in inflammatory conditions, hepatotoxicity and to determine the anti-diabetic and anti-trichomonal properties of the plant. MATERIALS AND METHOD: Anti-trichomonal, in vivo and in vitro antidiabetic and insulin stimulating, anti-inflammatory, hepatoprotective and anti-oxidant activities using Trichomonas gallinae, glucose loaded rats and in vitro insulin secreting cell line (INS-1 cell), carrageenin-induced rat paw oedema, CCl(4)-induced hepatotoxicity and DPPH scavenging ability methods respectively for the extracts and some isolates were determined. RESULTS: A dichloromethane extract was superior over methanolic extract with respect to an anti-trichomonal activity which was measured after 24 and 48 h. The isolated compounds imperatorin and 3-formylcarbazole had the main anti-trichomonal activity (LC(50)s of 6.0, 3.0 and 3.6, 9.7 microg/mL after 24 and 48 h, respectively). Methanolic extract (100 mg/kg) induced maximum and significant (p<0.05) anti-hyperglycaemic activity of 15.8% at 30 min and a 38.5% increase in plasma insulin at 60 min, compared to control. The increase in plasma insulin after 60 min, compared to 0 min, was 62.0% (p<0.05). The significant 174.6% increase of insulin release from INS-1 cells (in vitro) at 0.1 mg/ml indicates that it mediates its antidiabetic action mainly by stimulating insulin release. Imperatorin and chalepin were the major active constituents increasing in vitro insulin release to 170.3 and 137.9%, respectively. 100 mg/kg of the methanolic extract produced an anti-inflammatory activity after 4 h. A sedative effect was not observed. 100 and 200 mg/kg of methanolic extract administered i.p., reduced CCl4-induced hepatotoxicity firstly by 5.3 and 8.4% reduction in phenobarbitone-sleeping time respectively, secondly by reversing the reduction in serum liver proteins by 7.0-8.8%, serum AST, ALT and ALP activities by 27.7-107.9% and thirdly by diminishing increased values of plasma AST, ALT and ALP activities by 13.2-83.8%. The extract exhibited antioxidant activities. CONCLUSION: The hepatoprotective activity of C. lansium is partly due to its anti-oxidant and anti-inflammatory properties and confirms its folkloric use in the treatment of gastro-intestinal inflammation, bronchitis and hepatitis. In addition the use of C. lansium stem bark would be useful in diabetes and trichomoniasis.
Asunto(s)
Antiinflamatorios/farmacología , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Clausena , Edema/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Extractos Vegetales/farmacología , Trichomonas/efectos de los fármacos , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/uso terapéutico , Glucemia , Proteínas Sanguíneas/metabolismo , Carbazoles/aislamiento & purificación , Carbazoles/farmacología , Línea Celular , Clausena/química , Enzimas/sangre , Furocumarinas/aislamiento & purificación , Furocumarinas/farmacología , Hipnóticos y Sedantes/farmacología , Insulina/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Fitoterapia , Corteza de la Planta , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Tallos de la Planta , Ratas , Ratas WistarRESUMEN
The diagnosis and treatment of irritable bowel syndrome (IBS) are complicated. Artichoke extracts are well known to be helpful in various gastrointestinal disorders. A hydrophilic extract 36_U mainly containing luteolin-7-glycoside, luteolin-7-O-glucoside, small amounts of cynarin and luteolin increased contraction of rat ileum. This is mainly mediated by 5-HT(3) - and 5-HT(2) receptors but not 5-HT(4) receptors as can be derived by using specific antagonists such as tropisetrone, GR113806 and ketanserine. Additional mechanisms (receptors) are involved since the combination of these three antagonists was not able to fully prevent the contractive effect of extract 36_U. The lipophilic extract 36_EB mainly containing cynarin, luteolin including its glycosides, and cholorogenic acid in contrast to extract 36_U had a relaxing effect which could hardly be washed out. It was diminishing a serotonin effect and was not modified by ACh or substance P. The peristaltic threshold, i.e. the distension necessary for inducing a pathophysiologically relevant propulsion activity, is one of the important features being correlated with IBS. The peristaltic threshold was decreased by both serotonin and extract U_36. From the data it can be derived that the extract 36_U may be useful in IBS combined with obstipation when gastrointestinal contraction is necessary, whereas 36_EB may be useful in IBS combined with diarrhea when gastrointestinal relaxation is desired. Especially interesting are the influence on the threshold. It would be interesting to know which effects are mediated via cynarin and luteolin or its glycosides.
Asunto(s)
Cynara scolymus/química , Íleon/efectos de los fármacos , Peristaltismo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Atropina/farmacología , Cinamatos/farmacología , Femenino , Flavonas/farmacología , Glucósidos/farmacología , Indoles/farmacología , Síndrome del Colon Irritable/fisiopatología , Luteolina/farmacología , Masculino , Contracción Muscular/efectos de los fármacos , Ratas , Receptores de Serotonina/metabolismo , Serotonina/metabolismo , Serotonina/farmacología , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología , TropisetrónRESUMEN
NIGELLA SATIVA L. has many effects including those on the gastrointestinal tract and trachea and is, therefore, used in the Mediteranean area and in India/Pakistan. Our aim was to investigate the effect of two main constituents, nigellone and thymoquinone, on trachea (antispasmodic effect) and their influence on respiratory clearance. The effects on Ba (2+)-, carbachol- and leukotriene-induced trachea contractions and the transport of the fluorescence dye rhodamin B concerning ciliary action in the tracheal area were investigated using a microdialysis technique. Nigellone and high concentrations of thymoquinone had a concentration-dependent inhibitory effect on the trachea when being contracted by the depolarizing effect of Ba (2+). The trachea contractions induced by leukotriene-d (4) were inhibited by nigellone and by thymoquinone. The cholinergic system (stimulation by carbachol) was hardly involved. The rate of ciliary clearance (mucociliary transport) was slightly modified by a high thymoquinone concentration (153.0 vs. 505.0 sec/12 mm distance, respectively), and was highly increased by nigellone (217.5 vs. 505.0 sec/12 mm distance). In conclusion, this study provides evidence for an antispasmodic effect and an increase in mucociliary clearance for nigellone but not for thymoquinone. Altogether the data indicate that nigellone but not thymoquinone may be useful in treatment of different respiratory diseases.
Asunto(s)
Benzoquinonas/farmacología , Depuración Mucociliar/fisiología , Tráquea/fisiología , Animales , Compuestos de Bario/farmacología , Benzoquinonas/aislamiento & purificación , Cloruros/farmacología , Leucotrieno D4/farmacología , Ratones , Ratones Endogámicos C57BL , Depuración Mucociliar/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Nigella sativa , Ratas , Tráquea/efectos de los fármacosRESUMEN
Anti-adhesive compounds are potential prophylactic tools in alternative treatment regimes against bacterial infection, as bacterial adhesion is commonly mediated by carbohydrate-protein interactions between surface adhesions of microorganisms and the host cell. The use of exogenous polyvalent, high-molecular carbohydrates and tannin-like plant-derived compounds should antagonize the adhesive interaction. A range of carbohydrates and carbohydrate- and proanthocyanidin-enriched plant extracts were screened for potential anti-adhesive effects against Helicobacter pylori, Campylobacter jejuni, Porphyromonas gingivalis and Candida albicans in different in-situ assays on primary tissue. The adhesion of H. pylori on human stomach tissue was effectively blocked by glucuronic acid-enriched polysaccharides from immature okra fruits (Abelmoschus esculentus). These compounds also had strong in-vitro effects against C. jejuni (inhibition up to 80%), but were ineffective in an in-vivo study in infected chicken broilers due to metabolism in the gastrointestinal system. Polysaccharides from Glycyrrhizia glabra, also enriched with glucuronic acid, showed strong anti-adhesive properties against H. pylori and P. gingivalis (inhibition 60-70%). Pelargonium sidoides extract, containing mainly polymeric proanthocyanidins, was effective against H. pylori in a dose-dependent manner. Due to the multifunctional adhesive strategy of C. albicans, no effective compounds were detected against this yeast. Structure-activity relationships are presented and the potential in-vivo use of carbohydrate-based anti-adhesives is discussed.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Adhesión Bacteriana/efectos de los fármacos , Abelmoschus/química , Animales , Campylobacter jejuni/efectos de los fármacos , Campylobacter jejuni/fisiología , Candida albicans/efectos de los fármacos , Candida albicans/fisiología , Carbohidratos/aislamiento & purificación , Carbohidratos/farmacología , Pollos , Mucosa Gástrica/microbiología , Glycyrrhiza/química , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/fisiología , Humanos , Pelargonium/química , Extractos Vegetales/farmacología , Polisacáridos/administración & dosificación , Polisacáridos/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Porphyromonas gingivalis/fisiología , Proantocianidinas/análisis , Ratas , Relación Estructura-ActividadRESUMEN
UNLABELLED: Thyme is a broncholytic und secretomotoric agent. Thus, our aim was to investigate the influence of a thyme extract on beta (2)-receptors in competition binding experiments and relaxation experiments on rat uteri and trachea. Furthermore, the influence of the extract on respiratory clearance was of interest. Binding experiments were performed using purified rat lung membranes with the beta(2)-receptor ligand [(125)I]-CYP {[(125)I]-(+/-)-Iodocyanopindolol}. The transport of the fluorescence dye rhodamin 123 concerning ciliary action in the tracheal area of a mouse was investigated using a microdialysis technique. The thyme extract reduces only slightly [(125)I]-CYP binding and amplifies the displacement of [(125)I]-CYP by propranolol (non-specific beta-receptor antagonist): the displacement curve in the concentration range representing beta (2)-receptors (nM) is shifted to the left. Thyme extract had relaxing effects on organs possessing beta (2)-receptors (uterus and trachea). The propranolol-induced antagonism to isoprenaline is reverted concentration-dependently by the extract. A duplication of the rate of ciliary clearance by the extract was observed. IN CONCLUSION: 1) There is evidence for an influence of a thyme extract on beta (2)-receptors by both binding studies and biological effects: As can be derived from the shift of the propranolol displacement curve (nM), ingredients of the thyme extract slightly interact with beta (2)-receptors in rat lung tissue. This effect is indirect since no full range competition curve was reached. 2) An at least indirect interaction with beta (2)-receptors in rat uteri and trachea is revealed by a decreased antagonism of propranolol on the relaxing effect of isoprenaline by the plant extract. 3) An additional mechanism is presumed because at high extract concentrations isoprenaline-induced relaxation is complete, whereas the displacement of propranolol at beta (2)-receptors is only weak. 4) Thyme extract has an indirect (modulatory) effect on the beta (2)-receptor system. 5) Mucociliary clearance is improved in vivo. Its mechanism has still to be elucidated.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Thymus (Planta) , Tráquea/efectos de los fármacos , Contracción Uterina/efectos de los fármacos , Agonistas Adrenérgicos beta/administración & dosificación , Agonistas Adrenérgicos beta/uso terapéutico , Antagonistas Adrenérgicos beta , Animales , Relación Dosis-Respuesta a Droga , Femenino , Ratones , Ratones Endogámicos C57BL , Depuración Mucociliar/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Propranolol , Ratas , Ratas Wistar , Receptores Adrenérgicos beta 2/efectos de los fármacosRESUMEN
A contribution of the volatile oil from ginger rhizomes (Zingiber officinale Roscoe) on inhabiting the 5-HT3 receptor complex had been shown. In the present study a possible interaction of some compounds of the volatile oil with the 5-HT3 receptor system expressed in N1E-115 cells and with the serotoninergic system of the rat ileum was investigated. The volatile oil was obtained by steam distillation and fractionated using a silica gel column resulting in five fractions. Compounds of the fractions were identified by GC-MS. The influence of the volatile oil, its fractions and pure components on serotonin-induced [14C]guanidinium influx into N1E-115 cells was measured indicating the inhibitory interaction with the 5-HT3 receptor channel system. Most potent inhibitors of cation influx were the volatile oil, fraction 4, beta-pinene, terpinolene, alpha-copaene and alpha-phellandrene. The volatile oil and fractions 1 and 4 were not able to significantly influence either serotonin (10 microM)-induced maximum contraction of the rat ileum or the second phase of the biphasic contraction 2.5 min after serotonin addition. However, beta-pinene, terpinolene and alpha-phellandrene reduced both contractions. In conclusion, the volatile oil and distinct compounds such as terpinolene, beta-pinene and alpha-phellandrene interact with 5-HT3 receptor channel system and possess an antispasmodic effect at the rat ileum.
Asunto(s)
Íleon/efectos de los fármacos , Aceites de Plantas/farmacología , Antagonistas del Receptor de Serotonina 5-HT3 , Antagonistas de la Serotonina/farmacología , Zingiber officinale , Animales , Línea Celular Tumoral/efectos de los fármacos , Línea Celular Tumoral/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Íleon/metabolismo , Ratones , Neuroblastoma/patología , Aceites de Plantas/administración & dosificación , Aceites de Plantas/uso terapéutico , Ratas , Receptores de Serotonina 5-HT3/metabolismo , Rizoma , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/uso terapéuticoRESUMEN
The aqueous infusion (tea) of Stachytarpheta cayennensis leaves is used ethnomedically in Peru, Nigeria and other tropical countries for the management of diabetes. Oral administration (p. o.) of aqueous (125 mg/kg) and methanolic (2000 mg/kg) extracts of the leaves to alloxan-diabetic rats showed significant blood glucose reductions by 43 and 53%, respectively, at the end of a 4 hour period similar to the strong effect of glibenclamide (5 mg/kg, P. O.). The methanolic extract was successively partitioned into ethyl acetate, butanol and water fractions, and the same test showed that the butanol fraction (2000 mg/kg) had the highest (50%) hypoglycaemic activity at 4 hours after oral administration. It was also the most active fraction when tested in vitro [insulin release from an insulin secreting cell line (INS-1)] and was also active in normal rats and rats made hyperglycaemic by a glucose load. Its activity was comparable to that of glibenclamide (positive control) in these models. This active butanol fraction was subjected to chromatographic subfractionation; some subfractions reduced hyperglycaemia in alloxan-diabetic rats to 60 and 78% and induced insulin release from the INS-1 cells; other subfractions, however, gave hyperglycaemic activities IN VIVO and inhibition of insulin release from the INS-1 cells. Three major compounds of the butanol fraction were isolated and characterised as 6beta-hydroxyipolamide, ipolamide and isoverbascoside; they increased insulin secretion from INS-1 cells to 125, 128 and 127%, respectively, whereas glibenclamide increased insulin secretion to 157%. The results justify the ethnomedical use of the plant in the management of diabetes and suggest that the butanol fraction and some of its isolated constituents mediate their actions primarily by stimulating insulin release directly.
Asunto(s)
Hipoglucemiantes/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Verbenaceae , Administración Oral , Aloxano , Animales , Glucemia/efectos de los fármacos , Línea Celular Tumoral/efectos de los fármacos , Línea Celular Tumoral/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Glucosa , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Insulina/metabolismo , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Ratas , Ratas WistarRESUMEN
An ethanolic spissum extract of the aerial parts of Plantago lanceolata L. was examined for antispasmodic activity on isolated ileum and trachea of the guinea-pig. Isolated constituents were investigated as well. The P. lanceolata extract inhibited the contractions of the guinea-pig ileum that were induced by various agonists such as acetylcholine (ACh), histamine, potassium and barium ions. Additionally the trachea contractions induced by barium ions were inhibited. The compounds luteolin, acteoside, plantamajoside an catalpol peracetate but not catalpol, isoacteoside, lavandulifolioside and aucubin inhibited the ACh-induced contractions of the guinea-pig ileum. Luteolin and acteoside reduced the barium-induced contractions of the guinea-pig trachea. Two recently isolated compounds did not show antispasmodic activity: luteolin-3',7-diglucuronide and beta-hydroxy-acteoside.
Asunto(s)
Contracción Muscular/efectos de los fármacos , Plantago/química , Espasmo/tratamiento farmacológico , Acetilcolina/farmacología , Animales , Bario/farmacología , Femenino , Cobayas , Histamina/farmacología , Íleon/efectos de los fármacos , Masculino , Extractos Vegetales/química , Extractos Vegetales/farmacología , Potasio/farmacología , Espasmo/fisiopatología , Tráquea/efectos de los fármacosRESUMEN
Different extracts (ethanolic, hexane, aqueous) of ginger (rhizomes of Zingiber officinale) and the essential oil were tested using [14C]guanidinium influx into N1E-115 cells and the isolated rat ileum in order to identify their activity in inhibiting 5-HT3 receptor function. The hexane extract proved to be the most active and yielded upon bioassay-guided fractionation nine constituents: [6]-, [8]-, [10]-gingerols, [6]- and [8]-shogaols which were previously shown as active in vivo against cytotoxic drug-induced emesis; [4]-gingerol, [6]-gingerdiol, diacetyl-[6]-gingerdiol and [6]-dehydrogingerdione have not been previously tested for anti-emetic or 5-HT3 receptor antagonistic effects. Even though the latter four compounds are only minor constituents, their identification contributed towards the characterisation of a structure-activity relationship of this class of compounds. The order of potency for the nine constituents in the N1E-115 cell system was [6]-gingerdiol approximately diacetyl-[6]-gingerdiol approximately [6]-dehydrogingerdione approximately [6]-shogaol > or = [8]-shogaol approximately [8]-gingerol > [10]-gingerol > or = [6]-gingerol > [4]-gingerol.
Asunto(s)
Fitoterapia , Extractos Vegetales/farmacología , Aceites de Plantas/farmacología , Receptores de Serotonina 5-HT3/efectos de los fármacos , Antagonistas de la Serotonina/farmacología , Zingiber officinale , Animales , Línea Celular Tumoral/efectos de los fármacos , Línea Celular Tumoral/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Íleon/efectos de los fármacos , Masculino , Ratones , Neuroblastoma , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Aceites de Plantas/administración & dosificación , Aceites de Plantas/uso terapéutico , Ratas , Rizoma , Antagonistas del Receptor de Serotonina 5-HT3 , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/uso terapéuticoRESUMEN
Diabetic disease is increasing rapidly and vast amounts of resources are spent in all countries. Thus, the screening of new compounds including plant extracts for antidiabetic effects is mandatory. In this review both simple assays [e.g., on blood glucose (after or without a glucose load), plasma insulin and extrapancreatic effects] are described as well as specific in vivo tests in diabetic animals and in vitro tests with respect to the mechanism of compounds. In total, approx. 30 selected tests are evaluated and references are given. Thus, the investigator is guided through the tests and is advised that measuring only one parameter such as glucose will not be sufficient. In the case that the financial resources are poor for the investigator, more than glucose still has to be measured. A balance is made by describing absolutely necessary investigations while concentrating on those at low cost. It has to be started with simple assays; to use one test only, however, means oversimplifying the diabetes disease; additionally antidiabetic effects may be missing. The investigator is guided through the advantages and limitations of diabetic animal models and is advised about specific in vitro tests to look at the mechanism of action. All investigators should profit from these details, not only the phytoresearchers.
Asunto(s)
Glucemia , Hipoglucemiantes/farmacología , Insulina/sangre , Animales , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Hipoglucemiantes/uso terapéutico , Modelos Animales , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
The crude extracts of Chelidonium majus and Corydalis lutea were examined for antispasmodic activity against acetylcholine (ACh)-induced contraction on isolated rat ileal smooth muscle. Further, coptisine and caffeolmalic acid as components of the alkaloid and the hydroxycinnamic acid ester fraction of both plants were similarly investigated. The ACh-induced contraction was found to be antagonized weakly by caffeolymalic acid (6.9%; 2.5 x 10(-5) g/ml/organ bath), C. majus extract (12.7%; 2.0 x 10(-4) g/ml), and a higher concentration of coptisine (16.5%; 1.0 x 10(-5) g/ml) whereas the antispasmodic activity of C.lutea extract reached 45% (2.0 x 10(-4) g/ml). Antagonism by papaverine as a positive control amounted to 83.2%.
Asunto(s)
Acetilcolina/farmacología , Berberina/análogos & derivados , Ácidos Cafeicos/farmacología , Malatos/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso/fisiología , Extractos Vegetales/farmacología , Plantas Medicinales , Animales , Berberina/farmacología , Íleon , Técnicas In Vitro , Músculo Liso/efectos de los fármacos , RatasRESUMEN
In a double-blind crossover trial, the effect of 4 week daily ingestion of eight cups of regular coffee (corresponding to 504 mg caffeine) vs eight cups of decaffeinated coffee was studied. Blood pressure, heart rate and urinary catecholamines were measured in eight healthy, young volunteers. In both groups, regular coffee immediately led to a significant increase in mean blood pressure (+ 3 and + 5 mm Hg respectively). The difference between both groups, however, existed only in the first 3 to 5 days of ingestion of regular coffee. On day 5 after ingestion of regular coffee, and thereafter in weekly intervals, no significant increase in catecholamine excretion was observed. The data suggest that long-term consumption of large amounts of coffee leads to only a small and transient rise in mean blood pressure. This may be due to an adaptation phenomenon. Therefore, continuous heavy coffee ingestion (eight cups/day for 4 weeks) by young persons does not appear to involve a risk of the development of hypertension.