RESUMEN
A phytopharmaceutical containing an extract of Echinacea purpurea and Glycyrrhiza glabra root (Revitonil tablets) was investigated for its suggested immunostimulating potential, using several in vitro tests and the in vivo carbon-clearance model in mice. In the in vitro phagocytosis test with human granulocytes, Revitonil showed a 44-53% stimulating effect at a concentration of 100 microg/ml. Whereas in the chemoluminescence test at a concentration of 1.25 microg/ml, Revitonil tablets exhibited a moderate enhancing effect only, a remarkable stimulating activity (30-50%) was observed in the T-lymphocyte CD69 bioassay at a concentration of 100 microg-1 microg/ml. The highest immunological efficacy could be assigned to Revitonil as revealed by the in vivo carbon-clearance model in mice. With RCt/RCc-values of 2.0, Revitonil exhibited a very high carbon elimination rate at oral administration. Because the Echinacea and Glycyrrhiza monoextracts alone showed lower RCt/RCc-values (1.3-1.7) than Revitonil, a potentiating synergistic effect of the extract mixture in Revitonil can be postulated.
Asunto(s)
Echinacea/química , Glycyrrhiza/química , Linfocitos/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Cromatografía Líquida de Alta Presión , Citometría de Flujo , Técnicas In Vitro , Linfocitos/inmunología , Fagocitosis/efectos de los fármacos , Comprimidos/químicaRESUMEN
A complex polysaccharide, Ths-3, consisting mainly of rhamnopyranosyl and galactofuranosyl units, has been isolated from the water extract of the lichen Thamnolia subuliformis using ethanol fractionation, dialysis, ion-exchange chromatography, gel filtration and preparative GP-HPLC. The mean M(r) of Ths-3 was determined to be 1450 kD, and the monosaccharide composition is gal/rha/glc/xyl/man in the ratio of 40:31:13:10:6. The structure of Ths-3 was further elucidated by methylation analysis by GC-MS and NMR spectroscopy and found to be basically composed of (1-->3)-linked beta-D-galactofuranosyl units with branches on C6, and rhamnosyl units being predominantly (1-->2)-linked with branches on C3 and C4, while some units are (1-->3)-linked. Glucose, mannose and galactofuranose are found as terminal units and glucose and mannose are also (1-->4)-linked, while xylose is only present as terminal units. The trisaccharide xylglcglc was detected after partial hydrolysis of the polysaccharide. The immunomodulating activity of Ths-3 was tested in an in vitro phagocytosis assay and the classical anticomplementary assay, and proved to be active in both tests. The authors suggest the trivial name thamnolan for Ths-3.
Asunto(s)
Proteínas Inactivadoras de Complemento/farmacología , Vía Clásica del Complemento/efectos de los fármacos , Líquenes , Fagocitosis/efectos de los fármacos , Polisacáridos/farmacología , Cromatografía de Gases , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Cromatografía de Gases y Espectrometría de Masas , Humanos , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificaciónRESUMEN
A polysaccharide, Ci-3, resembling isolichenan except with a much higher degree of polymerization, has been isolated from the water extract, as well as from the alkali extract, of the lichen Cetraria islandica (L.) using ethanol fractionation, dialysis, ion-exchange chromatography and gel filtration. The mean M(r) of Ci-3 was determined to be 2000 kD, compared to 6-8 kD reported for isolichenan. The structure of Ci-3 was elucidated and found to be composed of (1-->3)- and (1-->4)-alpha-D-glucopyranosyl units in the ratio of 2:1, using methanolysis, methylation analysis, optical rotation and NMR spectroscopy. The immunomodulating activity of Ci-3 was tested in an in vitro phagocytosis assay and anti-complementary, and proved to be active in both tests.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Glucanos/farmacología , Líquenes/química , Adyuvantes Inmunológicos/aislamiento & purificación , Carbohidratos/análisis , Cromatografía en Gel , Cromatografía por Intercambio Iónico , Cromatografía en Capa Delgada , Proteínas Inactivadoras de Complemento/farmacología , Glucanos/aislamiento & purificación , Humanos , Técnicas In Vitro , Metanol , Metilación , Fagocitosis/efectos de los fármacosRESUMEN
Several polysaccharide fractions, isolated from a hot aqueous extract of Cetraria islandica (L.) Ach. by ethanol fractionation and ion-exchange chromatography, exerted significant in vitro anti-complementary activity and pronounced enhancement of in vitro granulocytic phagocytosis. Prior to aqueous extraction, low molecular weight compounds were removed from the plant material by organic extraction. An aqueous extract, prepared by the traditional method of briefly boiling the lichen directly with water, also exhibited significant anti-complementary and enhanced phagocytic activity. When tested for reticuloendothelial phagocytic activity in the in vivo carbon clearance test, the extract gave rise to a significant increase in the rate of colloidal carbon elimination. Results show, that in addition to an immunostimulating alkali-soluble galactomannan previously isolated from Iceland moss, the plant also contains water soluble polysaccharides, extractable by traditional methods, which exert immunomodulating effects.
RESUMEN
The present study describes the influence of hypericin of Hypericum perforatum on TPA- and LPS-induced arachidonic acid (AA) metabolism, as well as interleukin 1 α and nitric oxide (NO) production in human immunocompetent cells. The results show that hypericin inhibits the release of arachidonic acid (AA) from membrane phospholipids in calcium ionphore A23187-TPA stimulated human granulocytes in a dose-dependent manner (IC(50) 4 µM), but that calcium ionophore is not the only inducer. An inhibitory effect could be observed at concentrations of < 0.4 µM and in the presence of low concentrations of TPA (0.16 - 0.32 µM). As a result of this inhibition hypericin inhibits the release of LTB(4) but not of PGE(2). Hypericin also inhibits the production of IL-1α in LPS-stimulated human monocytes and activates NO production in isolated human leukocytes. This effect is comparable to the effect of LPS and is probably not associated with the IL 1 a or intermediates of the cycloxygenase pathway. The results as a whole let us assume that one important mechanism for the antiviral, antiinflammatory and antitumoral effects of hypericin and Hypericum extracts is the inhibition of the PKC-mediated signalling pathway which in turn influences the AA metabolism, and the interleukin-1 α production resulting in an immunosuppressive effect on the host immune system.
RESUMEN
This article describes and discusses five placebo-controlled randomized studies investigating the immunomodulatory activity of preparations containing extracts of Echinacea in healthy volunteers. A total of 134 (18 female and 116 male) healthy volunteers between 18 and 40 years of age were studied. Two studies tested intravenous homeopathic complex preparations containing Echinacea angustifolia D1 (study 1) and D4 (study 5). Two studies (2 and 3a) tested oral alcoholic extracts of roots of E. purpurea, one study an extract of E. pallida roots (study 3b), and one study an extract of E. purpurea herb (study 4). Test and placebo preparations were applied for four (study 5) or five (studies 1-4) consecutive days. The primary outcome measure for immunomodulatory activity was the relative phagocytic activity of polymorphonuclear neutrophil granulocytes (PNG), measured in studies 1 and 2 with a microscopic method and in studies 3, 4, and 5 with two different cytometric methods. The secondary outcome measure was the number of leukocytes in peripheral venous blood. Safety was assessed by a screening program of blood and other objective parameters as well as by documentation of all subjective side effects. In studies 1 and 2 the phagocytic activity of PNG was significantly enhanced compared with placebo [maximal stimulation 22.7% (95% confidence interval 17.5-27.9%) and 54.0% (8.4-99.6%), respectively], while in the other studies no significant effects were observed. Analysis of intragroup differences revealed significant changes in phagocytic activity during the observation periods in five test and three control groups. Leukocyte number was not influenced significantly in any study. Side effects due to the test preparations could not be detected. Our studies provide evidence for immunomodulatory activity of the homeopathic combination tested in study 1 and the E. purpureae radix extract tested in study 2. The negative results of the other three studies are difficult to interpret due to the different methods for measuring phagocytosis, the relevant changes in phagocytic activity within most placebo and treatment groups during the observation period, and the small sample sizes. Future studies should be performed on patients rather than healthy volunteers and use standardized or chemically defined monopreparations of Echinacea.
Asunto(s)
Adyuvantes Inmunológicos/normas , Antiinflamatorios no Esteroideos/inmunología , Granulocitos/efectos de los fármacos , Homeopatía/normas , Recuento de Leucocitos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Extractos Vegetales/inmunología , Adyuvantes Inmunológicos/química , Adolescente , Adulto , Antiinflamatorios no Esteroideos/química , Química Farmacéutica , Método Doble Ciego , Echinacea , Femenino , Citometría de Flujo , Humanos , Masculino , Extractos Vegetales/química , Método Simple CiegoRESUMEN
A new alkali-soluble polysaccharide has been isolated from Iceland moss, Cetraria islandica (L.) Ach., by ethanol fractionation, ion-exchange chromatography, and gel filtration. The mean M(r) was estimated to be 18,000. Sugar and methylation analysis, partial hydrolysis, and 13C-NMR spectroscopy showed the polysaccharide to be a branched galactomannan with a backbone composed of two structural elements; (1-->6)-linked alpha-D-mannopyranosyl and alpha-D-(1-->6)-galactopyranosyl units. The polysaccharide showed pronounced immunostimulating activity in an in vitro phagocytosis assay and in the in in vivo carbon clearance assay.
Asunto(s)
Líquenes/química , Mananos/farmacología , Fagocitosis/efectos de los fármacos , Secuencia de Carbohidratos , Galactosa/análogos & derivados , Granulocitos/efectos de los fármacos , Granulocitos/inmunología , Humanos , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Mananos/química , Mananos/aislamiento & purificación , Datos de Secuencia MolecularRESUMEN
Alcoholic extracts of the antipsoriatic Mahonia aquifolium drug which were analysed for their qualitative and quantitative alkaloid content, showed an in vitro inhibiting effect on cyclo-oxygenase (CO) of sheep seminal vesicles and 5-lipoxygenase (5-LO) of porcine leucocytes. The same extracts exhibited also immunostimulating activities in two phagocytosis assays. In contrast the major alkaloids of Mahonia aquifolium extracts berberine, palmatine, magnoflorine and jatrorrhizine were found to be inactive at all in both antiinflammatory assays, suggesting a different mechanism of action for the alkaloids or further not yet detected compounds in the extract.
RESUMEN
Extracts derived from Albizia amara were found to demonstrate activity in a recently developed hplc system designed to detect compounds capable of interacting with DNA. Further investigation led to the procurement of four sets of alkaloid isolates X1-X4 that were found to be macrocyclic pithecolobine alkaloids. All four isolates interacted with calf thymus DNA and were generally cytotoxic with a battery of cultured mammalian cells. As determined with Salmonella typhimurium strain TM677, isolates X1 and X3 were bactericidal, but not mutagenic. Isolate X1 was found to inhibit the catalytic activity of DNA polymerase, RNA polymerase, and HIV-1 reverse transcriptase. With DNA polymerase, the reaction was shown to be inhibited in a manner that was competitive with respect to DNA. In addition, isolate X1 inhibited each of the following: platelet aggregation, human lymphocyte transformation, phorbol-ester-induced chemiluminescence with human granulocytes, and cyclooxygenase activity. Detection of these alkaloids on the basis of their interaction with DNA exemplifies the validity of this approach.
Asunto(s)
Alcaloides/farmacología , ADN , Alcaloides/aislamiento & purificación , Animales , Antibacterianos , Antiinfecciosos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Cromatografía Líquida de Alta Presión/métodos , ARN Polimerasas Dirigidas por ADN/antagonistas & inhibidores , Ensayos de Selección de Medicamentos Antitumorales , Fabaceae/química , Granulocitos/efectos de los fármacos , VIH-1/efectos de los fármacos , VIH-1/enzimología , Humanos , Leucemia P388/tratamiento farmacológico , Linfocitos/efectos de los fármacos , Mutágenos/aislamiento & purificación , Mutágenos/farmacología , Inhibidores de la Síntesis del Ácido Nucleico , Plantas Medicinales , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Prostaglandina-Endoperóxido Sintasas/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa , Salmonella typhimurium/efectos de los fármacos , Células Tumorales CultivadasRESUMEN
The activity of phagocytosis was tested in the in vitro granulocyte test and the in vivo carbon-clearance-test in the mouse for an extract combination consisting of four plant extracts (Echinacea angustifolia, Eupatorium perfoliatum, Baptisia tinctoria and Arnica montana). In both immune models, a step by step stimulation of the activity of phagocytosis by the addition of the four plant extracts was shown with an increase in effectiveness of partially over 50% in comparison to the pure Echinacea angustifolia mono-extract. The extract combination showed also in both test models a higher efficiency than two other differently composed combination preparations and two Echinacea mono-preparations.
Asunto(s)
Fagocitosis/efectos de los fármacos , Plantas Medicinales/química , Animales , Combinación de Medicamentos , Granulocitos/efectos de los fármacos , Humanos , Técnicas In Vitro , Ratones , Extractos Vegetales/farmacología , Estimulación QuímicaRESUMEN
Ethanolic extracts of Echinacea purpurea, E. pallida and E. angustifolia roots were examined for immunological activity in the carbon clearance test with mice and in the granulocyte test. In the in vivo experiment all extracts, administered orally, were found to enhance phagocytosis significantly. These results correlate with the stimulation of phagocytosis in the in vitro granulocyte test. The lipophilic fractions of the extracts appeared to be more active than the polar fractions. All extracts were analyzed by HPLC in order to correlate the chemical constituents with the immunological activities.
Asunto(s)
Extractos Vegetales/farmacología , Plantas Medicinales/análisis , Animales , Cromatografía Líquida de Alta Presión , Femenino , Granulocitos/efectos de los fármacos , Granulocitos/inmunología , Ratones , Fagocitosis/efectos de los fármacos , Extractos Vegetales/análisisRESUMEN
The influence of a broad concentration range of naturally occurring naphthoquinones and other cytotoxic or cytostatic agents (azathioprine, colchicine, cyclophosphamide, fluorouracil, methotrexate and vincristine) on human granulocytes and lymphocytes was investigated in a systematic in vitro study. At high concentrations (100 micrograms-10 ng/ml) nearly all substances showed the known cytotoxic or immunosuppressive effects, whereas most of the same compounds displayed immunostimulating activities at very low concentrations (10 ng-10 fg/ml). After a cold shock or heat treatment lymphocytes became more sensitive against these compounds in the active concentration range than untreated cells. These results possibly give an explanation for the antitumour activity of some plant extracts, for which a direct cytotoxicity due to the applied low dose can be excluded.
Asunto(s)
Antineoplásicos/farmacología , Granulocitos/efectos de los fármacos , Linfocitos/efectos de los fármacos , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Técnicas In Vitro , Fagocitosis/efectos de los fármacos , Fitohemaglutininas/farmacología , Estimulación QuímicaRESUMEN
Four homeopathic drug preparations with extract dilutions between D1 and D30 (expression for the homeopathic grade of potencies) and some additives (minerals and animal toxins) were investigated, using two in vitro and one in vivo phagocytosis models. All preparations enhanced significantly the activity of phagocytosis in all used systems. In controlled prospective single-blind studies with the preparations C and D performed on 12 and 14 verum and 13 male placebo volunteers respectively with i.v. injections within a 5-day treatment the phagocytosis indices were measured during 11 days using the microscopic smear method. In both investigations the maximum of phagocytosis activity was reached between the 4th and 5th day of injection. After the 4th or 5th (next to the last or last) injection, a rapid decrease of activity occurred which reached normal values on the 11th day. Other laboratory parameters investigated were not influenced.
Asunto(s)
Granulocitos/efectos de los fármacos , Homeopatía , Fagocitosis/efectos de los fármacos , Adulto , Animales , Análisis Químico de la Sangre , Ensayos Clínicos como Asunto , Femenino , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Mediciones Luminiscentes , RatonesRESUMEN
From the stembark of OKOUBAKA AUBREVILLEI (+)-catechin, (-)-epicatechin, (+)-gallocatechin, (-)-epicatechingallate, (-)-epigallocatechingallate, gallic and protocatechuic acid have been isolated. The antimicrobial and immunostimulating activity of the drug extract were assigned to the phenolic compounds.
RESUMEN
From the roots of UNCARIA TOMENTOSA six oxindol alkaloids have been isolated and identified as isopteropodin, pteropodin, mitraphyllin, isomitraphyllin, rynchophyllin and isorynchophyllin. By ion pair chromatography on HPLC a fingerprint analysis has been worked out which allowed to differentiate between various UNICARIA-species and drug preparations. With the exception of mitraphyllin and rynchophyllin all alkaloids showed a pronounced enhancement effect on phagozytosis, determined in two IN VITRO tests and the IN VIVO-carbon clearance test.
RESUMEN
From the water or alcaline-water extracts of Echinacea purpurea (L.) Moench. and -angustifolia DC., Eupatorium cannabium L. and -perfoliatum L., Chamomilla recutita L. Rauscher, Calendula officinalis L., Baptisia tinctoria (L.) R. B., Achyrocline satureioides DC., Arnica montana L., Sabal serrulata Roem. et Schult., and Eleutherococcus (Acanthopanax) senticosus Maxim. polysaccharide fractions with molecular weights in the range of 25 000 to 500 000 and higher have been isolated, which, according to the granulocytes- and carbon clearance tests, showed significant immunostimulating activities. The isolated compounds belong to the group of watersoluble, acidic branched-chain heteroglycans. Their immunostimulating activity is compared and discussed with respect to other polysaccharides of biological activity.