RESUMEN
New oral treatments are needed for all forms of leishmaniasis. Here, the improved oral efficacy of quercetin (Qc) and its penta-acetylated derivative (PQc) was evaluated in cutaneous leishmaniasis after encapsulation in lipid-core nanocapsules (LNCs) of poly(ε-caprolactone). Leishmania amazonensis-infected BALB/c mice were given 51 daily oral doses of free drugs (16 mg kg-1) or LNC-loaded drugs (0·4 mg kg-1). While treatment with free Qc reduced the lesion sizes and parasite loads by 38 and 71%, respectively, LNC-Qc produced 64 and 91% reduction, respectively. The antileishmanial efficacy of PQc was similar but not as potently improved by encapsulation as Qc. None of the treatments increased aspartate aminotransferase, alanine aminotransferase or creatinine serum levels. These findings indicate that when encapsulated in LNC, Qc and, to a lesser extent, PQc can safely produce an enhanced antileishmanial effect even at a 40-fold lower dose, with implications for the development of a new oral drug for cutaneous leishmaniasis.
Asunto(s)
Leishmania mexicana/efectos de los fármacos , Nanocápsulas , Poliésteres/análisis , Quercetina/farmacología , Tripanocidas/farmacología , Animales , Femenino , Leishmaniasis Cutánea/tratamiento farmacológico , Lípidos/análisis , Ratones , Ratones Endogámicos BALB CRESUMEN
Leishmania amazonensis promastigotes are known to express furosemide (Lasix®)-sensitive P-type membrane Na+-ATPase. In the present study, furosemide activity was studied in intracellular amastigotes and infected BALB/c mice to investigate its efficacy in cutaneous leishmaniasis (CL). Intracellular parasites, but not macrophages, were found to be sensitive to killing by furosemide (IC50 = 87 µ m vs CC50 â« 1000 µ m, respectively). Although furosemide did not induce nitric oxide production or intracellular pH changes in infected macrophages, it led to a significant reactive oxygen species (ROS) burst. Freshly isolated tissue parasites expressed a high degree of Na+-ATPase activity that decreased with culture, indicative of a higher enzyme expression in amastigotes than in promastigotes. Both intraperitoneal and oral treatment of L. amazonensis-infected mice with furosemide dosages equivalent to that prescribed as a diuretic significantly reduced the parasite's growth compared with the situation in untreated mice. Combination with oral furosemide increased the efficacy and safety of intraperitoneal treatment with sodium stibogluconate (SSG). To summarize, furosemide control of intracellular leishmanial growth by means of parasite Na+-ATPase inhibition, and macrophage ROS activation may help explain its sole and SSG-combined therapeutic effect against murine CL.
Asunto(s)
Furosemida/farmacología , Leishmania/efectos de los fármacos , Tripanocidas/farmacología , Adenosina Trifosfatasas/antagonistas & inhibidores , Animales , Proteínas de Transporte de Catión/antagonistas & inhibidores , Diuréticos/farmacología , Femenino , Leishmaniasis Cutánea , Ratones , Ratones Endogámicos BALB CRESUMEN
Previously, we showed that treating macrophages with ATP impairs the intracellular growth of Leishmania amazonensis, and that the P2X7 purinergic receptor is overexpressed during leishmaniasis. In the present study, we directly evaluated the effect of periodate-oxidized ATP (oATP) on parasite control in Leishmania-infected macrophages. We found that oATP impaired the attachment/entrance of L. amazonensis promastigotes to C57BL/6 mouse macrophages in a P2X7 receptor-independent manner, as macrophages from P2X7(-/-) mice were similarly affected. Although oATP directly inhibited the growth of axenic promastigotes in culture, promoted rapid ultrastructural alterations, and impaired Leishmania internalization by macrophages, it did not affect intracellular parasite multiplication. Upon infection, phagosomal acidification was diminished in oATP-treated macrophages, accompanied by reduced endosomal proteolysis. Likewise, MHC class II molecules expression and ectoATPase activity was decreased by oATP added to macrophages at the time of parasite infection. These inhibitory effects were not due to a cytotoxic effect, as no additional release of lactate dehydrogenase was detected in culture supernatants. Moreover, the capacity of macrophages to produce nitric oxide and reactive oxygen species was not affected by the presence of oATP during infection. We conclude that oATP directly affects extracellular parasite integrity and macrophage functioning.
Asunto(s)
Adenosina Trifosfato/análogos & derivados , Leishmaniasis/tratamiento farmacológico , Leishmaniasis/inmunología , Macrófagos/inmunología , Receptores Purinérgicos P2X7/genética , Adenosina Trifosfato/farmacología , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/parasitología , Antígenos de Histocompatibilidad Clase II/biosíntesis , L-Lactato Deshidrogenasa/metabolismo , Leishmania/inmunología , Leishmaniasis/parasitología , Macrófagos/parasitología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico/biosíntesis , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Aqueous extract of Kalanchoe pinnata (Kp) have been found effective in models to reduce acute anaphylactic reactions. In the present study, we investigate the effect of Kp and the flavonoid quercetin (QE) and quercitrin (QI) on mast cell activation in vitro and in a model of allergic airway disease in vivo. Treatment with Kp and QE in vitro inhibited degranulation and cytokine production of bone marrow-derived mast cells following IgE/FcÉRI crosslinking, whereas treatment with QI had no effect. Similarly, in vivo treatment with Kp and QE decreased development of airway hyperresponsiveness, airway inflammation, goblet cell metaplasia and production of IL-5, IL-13 and TNF. In contrast, treatment with QI had no effect on these parameters. These findings demonstrate that treatment with Kp or QE is effective in treatment of allergic airway disease, providing new insights to the immunomodulatory functions of this plant.
Asunto(s)
Hiperreactividad Bronquial/tratamiento farmacológico , Kalanchoe/química , Mastocitos/efectos de los fármacos , Fitoterapia , Quercetina/análogos & derivados , Animales , Prueba de Desgranulación de los Basófilos , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/prevención & control , Células Caliciformes/efectos de los fármacos , Células Caliciformes/inmunología , Interleucina-13/inmunología , Interleucina-5/inmunología , Kalanchoe/inmunología , Mastocitos/inmunología , Metaplasia/tratamiento farmacológico , Metaplasia/inmunología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Extractos Vegetales/química , Quercetina/inmunología , Quercetina/aislamiento & purificación , Quercetina/farmacología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
The interest in developing new sunscreens is increasing due to the harmful effects of UV radiation on the skin, such as erythema, accelerated skin ageing (photoageing) and the induction of skin cancer. However, many molecular sunscreens penetrate into the skin causing photoallergies, phototoxic reactions and skin irritation. Thus, the aim of this work was the preparation and characterization of polymeric and solid lipid nanoparticles to act carriers of benzophenone-3 (BZ3), aiming to improve the safety of sunscreen products by increasing the sun protection factor (SPF), decreasing BZ3 skin penetration and decreasing BZ3 concentration in sunscreen formulation. BZ3 was encapsulated in poly(epsilon-caprolactone) (PCL) nanoparticles by the nanoprecipitation method and in solid lipid nanoparticles (SLN) by the hot high pressure homogenization method. The particles were stable for 40 days. The BZ3 encapsulated in PCL nanoparticles was released faster than BZ3 encapsulated in SLN. The sun protection factor increased when BZ3 was encapsulated in both nanostructures. However, BZ3 encapsulated in PCL nanoparticles decreased its skin permeation more than SLN-BZ3. Furthermore, BZ3 encapsulated in SLN did not exhibit cytotoxic or phototoxic effects in human keratinocytes (HaCaT cells) and BABL/c 3T3 fibroblasts, whereas PCL nanoparticles with BZ3 showed phototoxic potential in HaCaT cells. Nevertheless, BZ3 free and encapsulated in PCL nanoparticles or in SLN did not show allergic reactions in mice. Our results suggest that these nanostructures are interesting carriers for sunscreen.
Asunto(s)
Lípidos/química , Nanocápsulas/química , Polímeros/química , Absorción Cutánea/fisiología , Piel/efectos de los fármacos , Protectores Solares/química , Protectores Solares/farmacocinética , Administración Tópica , Animales , Humanos , Ratones , Nanocápsulas/administración & dosificación , Protectores Solares/administración & dosificaciónRESUMEN
Previously, we described the protective action of the immunomodulatory extract of Kalanchoe pinnata (Kp) in murine and human cutaneous leishmaniasis. In the present study, we investigated the effectiveness of Kp against visceral leishmaniasis, using the BALB/c mouse model of infection with Leishmania chagasi. Mice receiving oral daily doses of Kp (400 mg/kg) for 30 days displayed significantly reduced hepatic and splenic parasite burden, when compared with untreated animals. Protectiveness was accompanied by a reduction in parasite-specific IgG serum levels, and impaired capacity of spleen cells to produce IL-4, but not IFN-gamma and nitric oxide upon antigen recall in vitro. The reference drug Pentostam (72 mg/kg) given by the intra-peritoneal route on alternate days produced an anti-leishmanial effect similar to oral Kp. Our findings show that the oral efficacy of Kp, seen previously in murine cutaneous leishmaniasis, extends also to visceral leishmaniasis caused by L. chagasi, a difficult to treat and lethal disease of man.
Asunto(s)
Kalanchoe/inmunología , Leishmania , Leishmaniasis Visceral/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Anticuerpos Antiprotozoarios/sangre , Células Cultivadas , Femenino , Interleucina-4/biosíntesis , Leishmaniasis Visceral/sangre , Hígado/parasitología , Ratones , Ratones Endogámicos BALB C , Hojas de la Planta/inmunología , Bazo/inmunología , Bazo/parasitologíaRESUMEN
Previously, we reported the immunosuppressive action of the aqueous extract of Kalanchoe pinnata (Kp) in mice. In the present study, we report on the protective effect of Kp in fatal anaphylactic shock, likewise a Th2-driven immunopathology, and the identification of its active component. Mice daily treated with oral Kp during hypersensitization with ovalbumin were all protected against death when challenged with the allergen, as compared with the 100% mortality in the untreated group. A single intraperitoneal dose 3 h prior to challenge was partially effective. Oral protection was accompanied by a reduced production of OVA-specific IgE antibodies, reduced eosinophilia, and impaired production of the IL-5, IL-10 and TNF-alpha cytokines. In vitro, Kp prevented antigen-induced mast cell degranulation and histamine release. Oral treatment with the quercitrin flavonoid isolated from Kp prevented fatal anaphylaxis in 75% of the animals. These findings indicate that oral treatment with Kp effectively downmodulates pro-anaphylactic inducing immune responses. Protection achieved with quercitrin, although not maximal, suggests that this flavonoid is a critical component of Kp extract against this extreme allergic reaction.
Asunto(s)
Anafilaxia/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Kalanchoe , Fitoterapia , Extractos Vegetales/uso terapéutico , Quercetina/análogos & derivados , Animales , Citocinas/biosíntesis , Eosinofilia/prevención & control , Inmunoglobulina E/biosíntesis , Activación de Linfocitos , Masculino , Mastocitos/fisiología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Quercetina/uso terapéutico , Ratas , Células Th2/inmunologíaRESUMEN
Sixteen not new aromatic compounds were prepared by one-pot reaction i.e. through Baylis-Hillman reaction and were the first time evaluated against promastigote Leishmania amazonensis and infected mammalian cells. Most of the compounds were selectively more active against amastigotes than the reference drug sodium stibogluconate (Pentostam, IC(50)=44.7 microM). We found that 3-hydroxy-2-methylene-3-(4-bromophenyl) propanenitrile (13) was the most active (IC(50)=12.5 microM) and safer compound (0.0 (0.9); % macrophage LDH release), being the lead compound.
Asunto(s)
Leishmania/efectos de los fármacos , Nitrilos/síntesis química , Tripanocidas/síntesis química , Animales , Técnicas In Vitro , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/parasitología , Ratones , Nitrilos/química , Nitrilos/farmacología , Relación Estructura-Actividad , Tripanocidas/química , Tripanocidas/farmacologíaRESUMEN
The murine model of ovalbumin (OVA)-induced allergy was used to evaluate the effectiveness of oral treatment with the leaf extract of Cissampelos sympodialis Eichl. (Menispermaceae) (CS) in the modulation of immunoglobulin E (IgE) production and T cell activation. CS treatment with doses ranging from 200 to 600 mg/Kg/day for 15 days before and during OVA-sensitization promoted reduction in total and OVA-specific serum IgE. CS at 400 or 600 mg/Kg/day also reduced paw edema induced by local OVA challenge. Daily intake of up to 600 mg/Kg of oral CS by BALB/c mice did not reduce weight gain, which is indicative of a lack of systemic toxicity. To assess the effect of CS treatment on T cell proliferative response to stimuli in vitro, the mitogenic response of spleen cells of treated and control animals were evaluated. Cells from CS-treated animals showed an elevated background proliferative response to concanavalin-A (Con-A) when compared to those from control animals. Oral intake of CS increased the in vitro production of IFN-gamma and IL-10 by Con-A stimulated cells. Mice treated with 200 mg/Kg/day CS showed increasing levels of IFN-gamma. These results show that oral treatment with Cissampelos sympodialis extract has an immunomodulatory effect, reducing allergy-associated responses possibly by a preferential activation of Th1-type cytokines.
Asunto(s)
Cissampelos , Citocinas/biosíntesis , Inmunoglobulina E/sangre , Ovalbúmina/toxicidad , Células TH1/efectos de los fármacos , Administración Oral , Animales , Edema/sangre , Edema/inducido químicamente , Edema/tratamiento farmacológico , Femenino , Inmunoglobulina E/biosíntesis , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta , Ratas , Ratas Wistar , Células TH1/metabolismoRESUMEN
The inhibiting activity of triterpenoids isolated from the methanolic extract of Pourouma guianensis (Moraceae) leaves is described for promastigotes and intracellular amastigotes of Leishmania amazonensis. Whereas the fractions containing apigenin, friedelin, epi-friedelinol, arjunolic acid, hyptatic acid B, stigmasterol and sitosterol were of no or relatively low inhibitory activity, fractions containing tormentic acid, 2alpha,3beta-dihydroxyursan-12-en-28-oic acid, 2alpha,3beta-dihydroxyolean-12-en-28-oic acid, oleanolic acid and ursolic acid were very potent in inhibiting promastigote growth at 100 microg/ml. Of the eleven isolated compounds, however, only ursolic acid and oleanolic acid showed high activity against intracellular amastigotes (IC50 value = 27 microg/ml and 11 microg/ml, respectively), which was superior to the control drug Glucantime (IC50 value = 83 microg/ml). The antileishmanial activity of oleanolic acid was directed against the parasite and not due to activation of nitric oxide intermediates by macrophages, but this triterpenoid also significantly inhibited the phagocytic capacity of those cells at concentrations above 40 microg/ml, indicating a cytotoxic effect. These results indicate that Pourouma guianensis contains many triterpenoids and some, such as ursolic and oleanolic acids, may serve as lead compounds for new antileishmanial drugs, but chemical modifications may be necessary to avoid unselective cytotoxicity.
Asunto(s)
Antiprotozoarios/farmacología , Leishmania/efectos de los fármacos , Moraceae , Fitoterapia , Extractos Vegetales/farmacología , Animales , Antiprotozoarios/administración & dosificación , Antiprotozoarios/uso terapéutico , Humanos , Concentración 50 Inhibidora , Leishmaniasis/tratamiento farmacológico , Ratones , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Triterpenos/administración & dosificación , Triterpenos/farmacología , Triterpenos/uso terapéuticoRESUMEN
Leishmaniasis is an extremely difficult disease to treat. Previously, it was shown that oral Kalanchoe pinnata (Kp) leaf extract is strongly effective against murine leishmaniasis. Here, it is shown that the serum levels of alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), urea and alkaline phosphatase were unchanged in mice orally treated with supraoptimal Kp doses for 30 days, indicating the absence of chronic toxicity to the liver, heart or kidney. Additionally, evidence is presented that human leishmaniasis may also be controlled with oral Kp. A 36-year-old man with an active cutaneous leishmaniasis was orally treated with 30 g wet weight of Kp leaves/day for 14 days. During the Kp treatment, the lesion stopped growing and slightly decreased. No adverse reactions or toxicity was observed. This study reports for the first time that Kalanchoe pinnata contains substances potentially active and safe for the oral treatment of human cutaneous leishmaniasis.
Asunto(s)
Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Kalanchoe , Leishmaniasis Cutánea/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Administración Oral , Adulto , Animales , Antiprotozoarios/administración & dosificación , Femenino , Mano , Humanos , Leishmaniasis Cutánea/patología , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/administración & dosificación , Hojas de la PlantaRESUMEN
Previously we demonstrated that Kalanchoe pinnata (KP) leaf extracts inhibited in vitro lymphocyte proliferation and showed in vivo immunosuppressive activity. Here we attempt to identify the immunosuppressive substances present in KP guided by the lymphoproliferative assays. From the ethanolic extract was purified a fraction (KP12SA) twenty-fold more potent to block murine lymphocyte proliferation than the crude extract. Chemical analysis by 1H- and 13C-NMR, IR and GC-MS of KP12SA (methylated sample) showed 89.3% of palmitic acid (C16), 10.7% of stearic acid (C18) and traces of arachidic (C20) and behenic acids (C22). This study provides evidence that fatty acids present in Kalanchoe pinnata may be responsible, at least in part, for its immunosuppressive effect in vivo.
Asunto(s)
Ácidos Grasos/farmacología , Inmunosupresores/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Linfocitos T/efectos de los fármacos , Animales , División Celular/efectos de los fármacos , Ácidos Grasos/aislamiento & purificación , Ratones , Ratones Endogámicos BALB C , Linfocitos T/citologíaRESUMEN
The inhibition of intracellular Leishmania amazonensis growth by 2', 6'-dihydroxy-4'-methoxychalcone (DMC) isolated from Piper aduncum was further enhanced after encapsulation of DMC in polymeric nanoparticles. Encapsulated DMC also showed increased antileishmanial activity in infected BALB/c mice, as evidenced by significantly smaller lesions and fewer parasites in the lesions.
Asunto(s)
Antiparasitarios/administración & dosificación , Chalcona/análogos & derivados , Leishmania/efectos de los fármacos , Poliésteres/administración & dosificación , Animales , Chalcona/administración & dosificación , Chalconas , Sistemas de Liberación de Medicamentos , Femenino , Leishmaniasis/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB CRESUMEN
We have previously shown that oral treatment with the leaf extract of the plant Kalanchoe pinnata (Kp) significantly decreases the lesion size and the parasite load in BALB/c mice infected with Leishmania amazonensis. Here we report on the mode of action of Kp, particularly on the induction of nitric oxide (NO) production by macrophages. We observed that Kp has no direct inhibitory activity on extracellular promastigotes, but effectively decreases the intracellular amastigote growth in a dose-related fashion. A 58% reduction in amastigote growth induced by 500 micrograms/ml Kp was associated with a 6-fold increase in the production of NO by the macrophages. IFN-gamma synergistically enhanced the NO-stimulating effect of Kp in culture. Co-treatment with the inducible NO synthase enzyme inhibitor L-NG-monomethyl-arginine abolished the antileishmanial effect of Kp in vitro and in L. amazonensis-infected BALB/c mice. These results indicate that the protective effect of Kp in leishmaniasis may not be due to a direct effect on the parasite itself but rather to activation of the reactive nitrogen intermediates pathway of macrophages.
Asunto(s)
Antiparasitarios/uso terapéutico , Leishmania/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Óxido Nítrico/biosíntesis , Fitoterapia , Plantas Medicinales/uso terapéutico , Animales , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Inhibidores Enzimáticos/farmacología , Leishmania/crecimiento & desarrollo , Leishmaniasis/tratamiento farmacológico , Lipopolisacáridos/antagonistas & inhibidores , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/parasitología , Ratones , Ratones Endogámicos BALB C/parasitología , Óxido Nítrico/antagonistas & inhibidores , omega-N-Metilarginina/farmacologíaRESUMEN
2',6'-Dihydroxy-4'-methoxychalcone (DMC) was purified from the dichloromethane extract of Piper aduncum inflorescences. DMC showed significant activity in vitro against promastigotes and intracellular amastigotes of Leishmania amazonensis, with 50% effective doses of 0.5 and 24 micrograms/ml, respectively. Its inhibitory effect on amastigotes is apparently a direct effect on the parasites and is not due to activation of the nitrogen oxidative metabolism of macrophages, since the production of nitric oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rather than increased with DMC. The phagocytic activity of macrophages was functioning normally even with DMC concentrations as high as 80 micrograms/ml, as seen by electron microscopy and by the uptake of fluorescein isothiocyanate-labeled beads. Ultrastructural studies also showed that in the presence of DMC the mitochondria of promastigotes were enlarged and disorganized. Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 micrograms of DMC/ml. These observations suggest that DMC is selectively toxic to the parasites. Its simple structure may well enable it to serve as a new lead compound for the synthesis of novel antileishmanial drugs.
Asunto(s)
Antiinfecciosos/farmacología , Chalcona/análogos & derivados , Chalcona/farmacología , Leishmania/efectos de los fármacos , Leishmaniasis Cutánea/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Antiinfecciosos/uso terapéutico , Antiparasitarios/farmacología , Antiparasitarios/uso terapéutico , Células Cultivadas , Chalcona/uso terapéutico , Chalconas , Macrófagos/efectos de los fármacos , Macrófagos/parasitología , Macrófagos/ultraestructura , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Extractos Vegetales/uso terapéutico , Plantas/metabolismoRESUMEN
The effect of a leaf extract from Kalanchoe pinnata (Kp) was investigated in BALB/c mice infected with Leishmania amazonensis. Oral treatment with Kp significantly delayed onset of disease as compared to untreated mice or mice receiving Kp by the intravenous or topical routes. When initiated at early stages of infection, daily oral doses of 8 mg prevented lesion growth and the effect was long-lasting, comparable to the reference antileishmanial drug Glucantime. The decreased lesion growth using the oral route was accompanied by a significant decrease in the number of viable parasites. Protection was accompanied by a diminished capacity of animals to develop delayed-type hypersensitivity and to produce specific antibodies.
Asunto(s)
Leishmaniasis/tratamiento farmacológico , Plantas Medicinales , Administración Oral , Animales , Formación de Anticuerpos/efectos de los fármacos , Hipersensibilidad Tardía , Inmunosupresores/uso terapéutico , Leishmaniasis/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/uso terapéuticoAsunto(s)
Separación Celular/métodos , ADN/biosíntesis , Animales , Costos y Análisis de Costo , Ratones , Timidina/metabolismo , TritioRESUMEN
Aqueous or ethanol extracts obtained from the leaves of Mikania glomerata (Asteraceae) and different species of Kalanchoe (Crassulaceae) or Alternanthera (Amaranthaceae) and from seeds of Paullinia cupana (Sapindaceae) blocked the capacity of human lymphocytes to proliferate in vitro. In all cases, a proliferative response induced by cocultivation of lymphocytes with phytohemagglutinin was inhibited even after depletion of phagocytic mononuclear cells by adherence. A flavonoid-enriched fraction from K. pinnata and an ethyl acetate fraction from A. tenella were 10 to 20-fold, respectively, more potent in inhibiting lymphocyte proliferation than their original crude extracts. In contrast, these fractions had no inhibitory action on human natural killer activity. Lymphocyte suppression by the extracts was not due to a cytotoxic effect. Pre-incubation with the highest extract concentrations did not affect the capacity of lymphocytes to proliferate, after removal of extracts from the medium. These results indicate a direct action of the extracts on lymphocytes. They also suggest that these medicinal plants may contain potential immunosuppressive substances that selectively act on activation steps of the cells of the immune system.
RESUMEN
The role of antigen-presenting cells in the differential expansion of TH1 and TH2 T cells in murine leishmaniasis was investigated. In general, macrophages preferentially induced gamma interferon and interleukin-2 secretion by syngeneic Leishmania-specific T cells, whereas B cells were more efficient in activating interleukin 4 production. B cells from susceptible BALB/c mice were better in inducing TH2 responses than B cells from resistant C57BL/6 mice, whereas macrophages from C57BL/6 mice were superior to BALB/c macrophages in inducing TH1 responses.