RESUMO
Uncaria tomentosa is a plant native to the Amazon that has immunomodulatory and antitumor properties due to the alkaloids found in the plant, being able to modify the immune response by potentiating or suspending the action of cytokines secreted by macrophages that induce the immune response, either by the classical route (M1) or through the alternative route (M2). Macrophages activated by M1 convert L-arginine into L-citrulline and nitric oxide (NO), whereas macrophages activated by the M2 pathway use the enzymatic activity of arginase to convert the same substrate into L-ornithine and urea. The aim of this work was to evaluate the immunostimulating activity of the crude hydroalcoholic extract from the bark of the U. tomentosa stem in RAW 264.7 macrophages. Concentrations of 0.2, 0.1 and 0.05 mg/mL of U. tomentosa extract associated with LPS, INF-γ and IL-4 inducers were tested by determining NO production and arginase enzyme activity. Nitric oxide production was enhanced by the extract when associated with LPS and LPS + INF-γ inducers. In the activity of the arginase enzyme, the extract decreased the stimulation of IL-4 on the enzyme, mainly at 0.2 mg/mL concentration. Therefore, it is concluded that the crude hydroalcoholic extract of the stem bark of U. tomentosa in RAW 264.7 cells, at a concentration of 0.2 mg/mL, showed considerable pro-inflammatory activity.
Assuntos
Unha-de-Gato , Arginase , Interleucina-4 , Lipopolissacarídeos/farmacologia , Óxido Nítrico , Macrófagos , Extratos Vegetais/farmacologiaRESUMO
Abstract Uncaria tomentosa is a plant native to the Amazon that has immunomodulatory and antitumor properties due to the alkaloids found in the plant, being able to modify the immune response by potentiating or suspending the action of cytokines secreted by macrophages that induce the immune response, either by the classical route (M1) or through the alternative route (M2). Macrophages activated by M1 convert L-arginine into L-citrulline and nitric oxide (NO), whereas macrophages activated by the M2 pathway use the enzymatic activity of arginase to convert the same substrate into L-ornithine and urea. The aim of this work was to evaluate the immunostimulating activity of the crude hydroalcoholic extract from the bark of the U. tomentosa stem in RAW 264.7 macrophages. Concentrations of 0.2, 0.1 and 0.05 mg/mL of U. tomentosa extract associated with LPS, INF-γ and IL-4 inducers were tested by determining NO production and arginase enzyme activity. Nitric oxide production was enhanced by the extract when associated with LPS and LPS + INF-γ inducers. In the activity of the arginase enzyme, the extract decreased the stimulation of IL-4 on the enzyme, mainly at 0.2 mg/mL concentration. Therefore, it is concluded that the crude hydroalcoholic extract of the stem bark of U. tomentosa in RAW 264.7 cells, at a concentration of 0.2 mg/mL, showed considerable pro-inflammatory activity.
Resumo A Uncaria tomentosa é uma planta nativa da Amazônia que possui propriedades imunomoduladoras e antitumorais devido aos alcaloides encontrados no vegetal, sendo capaz de modificar a resposta imune ao potencializar ou suspender a ação de citocinas secretadas por macrófagos que induzem a resposta imune, seja pela via clássica (M1) ou pela via alternativa (M2). Macrófagos ativados pela M1 converte L-arginina em L-citrulina e óxido nítrico (NO), já os macrófagos ativados pela via M2 utilizam a atividade enzimática da arginase para converter o mesmo substrato em L-ornitina e ureia. O trabalho teve como objetivo avaliar a atividade imunoestimuladora do extrato hidroalcoólico bruto da casca do caule da U. tomentosa em macrófagos RAW 264.7. Foram testadas as concentrações 0.2, 0.1 e 0.05 mg/mL do extrato de U. tomentosa associadas aos indutores LPS, INF-γ e IL-4, por meio da determinação da produção de NO e atividade da enzima arginase. A produção de óxido nítrico foi potencializada pelo extrato quando associado aos indutores LPS e LPS + INF-γ. Na atividade da enzima arginase, o extrato diminuiu a estimulação da IL-4 sobre a enzima, principalmente na concentração 0.2 mg/mL. Portanto, conclui-se que o extrato hidroalcoólico bruto da casca do caule de U. tomentosa em células RAW 264.7, na concentração 0.2 mg/mL, demostrou atividade pró-inflamatória considerável.
RESUMO
BACKGROUND: Choroidal neovascularization (CNV) is the main cause of severe visual loss in age-related macular degeneration (AMD). Heparin/heparan sulfate are known to play important roles in neovascularization due to their abilities to bind and modulate angiogenic growth factors and cytokines. Previously, we have isolated from marine shrimp a heparin-like compound with striking anti-inflammatory action and negligible anticoagulant and hemorrhagic activities. OBJECTIVES: To investigate the role of this novel heparin-like compound in angiogenic processes. METHODS AND RESULTS: The anti-angiogenic effect of this heparinoid in laser-induced CNV and in vitro models is reported. The compound binds to growth factors (FGF-2, EGF and VEGF), blocks endothelial cell proliferation and shows no cytotoxic effect. The decrease in proliferation is not related to cell death either by apoptosis or secondary necrosis. The results also showed that the heparinoid modified the 2-D network organization in capillary-like structures of endothelial cells in Matrigel and reduced the CNV area. The effect on CNV area correlates with decreases in the levels of VEGF and TGF-ß1 in the choroidal tissue. The low content of 2-O-sulfate groups in this heparinoid may explain its potent anti-angiogenic effect. CONCLUSIONS: The properties of the shrimp heparinoid, such as potent anti-angiogenic and anti-inflammatory activities but insignificant anticoagulant or hemorrhagic actions, point to this compound as a compelling drug candidate for treating neovascular AMD and other angioproliferative diseases. A mechanism for the anti-angiogenic effect of the heparinoid is proposed.
Assuntos
Heparina/química , Animais , Proliferação de Células , Sobrevivência Celular , Neovascularização de Coroide , Colágeno/química , Combinação de Medicamentos , Células Endoteliais/citologia , Feminino , Glicosaminoglicanos/química , Heterozigoto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Laminina/química , Neovascularização Patológica , Penaeidae , Proteoglicanas/química , Ratos , Ratos ZuckerAssuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Feprazona , Artropatias , Articulação do Joelho , Ensaios Clínicos como AssuntoRESUMO
Os autores apresentam um programa de estimulo ao aleitamento materno instituto no Hospital Universitario Regional do Norte do Parana, em Londrina desde 1977. O programa inclui alojamento conjunto, orientacao no bercario, retorno precoce em ambulatorio e enfase nas orientacoes sobre aleitamento materno no programa de puericultura. Avaliam os resultados obtidos com 257 maes de criancas de dois a 12 meses, submetidas as orientacoes deste programa.Concluem que houve um aumento do indice de aleitamento materno das criancas atendidas no Hospital Universitario de Londrina comparado com dados anteriores. Comentam, no entanto, que esse aumento nao deve ser atribuido unicamente a acao do programa de estimulo ao aleitamento materno, mas tambem a outras fatores