RESUMO
Species of the Vernonia genius are widely distributed across the world. In traditional communities, they are commonly used in popular medicine for the treatment of inflammatory diseases. The objective of the present study was to evaluate the anti-inflammatory activity of Vernonia polysphaera Baker hydroalcoholic extract. A λ-carrageenan-induced paw edema and peritonitis model was established in BALB/c mice. The in vitro activity of the extract was measured on LPS-stimulated RAW 264.7 cells. There was no toxic effect on mice or on the cells treated with the extract. Animals treated with V. polysphaera extract demonstrated inhibition of paw edema in comparison with the untreated animals at all the analyzed doses. In peritonitis, treatment with the extract at a dose of 500 mg/kg resulted in a lower total leukocyte count in the peritoneal fluid and blood and lower levels of IL-1ß, IL-6, TNF-α and PGE-2 than the control group. Cells treated with 50 and 100 µg/mL of the extract exhibited lower levels of nitrite and pro-inflammatory cytokine production and lower COX-2, NF-κB expression. The V. polysphaera extract demonstrated an anti-inflammatory effect, interfering with cell migration, reducing pro-inflammatory cytokine levels and COX-2 expression and consequent interference with PGE-2, as well as inhibiting NF-κB transcription.
Assuntos
Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Peritonite/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vernonia , Animais , Anti-Inflamatórios/farmacologia , Líquido Ascítico/efeitos dos fármacos , Líquido Ascítico/metabolismo , Carragenina , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Feminino , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Peritonite/induzido quimicamente , Peritonite/metabolismo , Extratos Vegetais/farmacologia , Células RAW 264.7RESUMO
The present study investigated the effects of a new bradykinin B(1) receptor antagonist, R-954, on the development of Ehrlich ascitic tumor (EAT) induced by the intraperitoneal inoculation of EAT cells in mice and the formation of a solid tumor by the subcutaneous injection of the cells in rat paw. The development of the tumor was associated with an increase in mouse total cell counts in bone marrow (10.8-fold), ascitic fluid (14.6-fold), and blood (12.6-fold). R-954 (2mg/kg, s.c.) significantly reduced the ascitic fluid volume (63.7%) and the mouse weight gain (30.5%) after 10 consecutive days of treatment. The B(1) antagonist as well as the anti-neoplasic drug vincristine also significantly inhibited the increase in total cell count in bone marrow, ascitic fluid, and blood. R-954 reduced significantly the total protein extravasation (57.3%), the production of nitric oxide (56%), PGE(2) production (82%), and TNFα release (85.7%) in mice peritoneal cavity whereas vincristine reduced the release of these inflammatory mediators by 84-94%. The increase in paw edema after intraplantar injection of EAT cells was reduced by approximately 52% by either R-954 or vincristine treatment. In conclusion, this study presents for the first time the antitumoral activity of a new bradykinin B(1) receptor antagonist on ascitic and solid tumors induced by Ehrlich cell inoculation in mice and rats.
Assuntos
Antagonistas de Receptor B1 da Bradicinina , Bradicinina/análogos & derivados , Carcinoma de Ehrlich/tratamento farmacológico , Vincristina/farmacologia , Animais , Antineoplásicos/farmacologia , Líquido Ascítico/citologia , Líquido Ascítico/efeitos dos fármacos , Líquido Ascítico/metabolismo , Contagem de Células Sanguíneas , Bradicinina/administração & dosagem , Bradicinina/farmacologia , Carcinoma de Ehrlich/patologia , Dinoprostona/metabolismo , Edema/patologia , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
The aim of this study was to investigate the effect of chronic treatment with C. multijuga oil on Ehrlich tumor evolution. C. multijuga was fractionated in a KOH impregnated silica gel column chromatography to give three distinct fractions, i.e., hexanic, chloroformic, and methanolic, mainly composed by hydrocarbon sesquiterpenes, oxygenated sesquiterpenes and acidic diterpenes, respectively. Results demonstrated that the C. multijuga oil, the hexanic, and chloroformic fractions did not develop toxic effects. The oil, hexanic and chloroformic fractions (doses varying between 100 and 200mg/kg) showed antineoplasic properties against Ehrlich ascitic tumor (EAT) and solid tumor during 10 consecutive days of treatment inhibiting ascitic tumor cell number, reverting medulla and blood cell counts to values similar to control group, and inhibiting the increase on several inflammatory mediators (total protein, PGE(2), nitric oxide, and TNF) on ascitic fluid. The treatment also inhibited the increase in paw volume on tumor-inoculated mice. In conclusion, C. multijuga as well as its fractions demonstrated antineoplasic effect even after oral administration confirming its use by traditional medicine.
Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Fabaceae/química , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Administração Oral , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Líquido Ascítico/efeitos dos fármacos , Líquido Ascítico/metabolismo , Contagem de Células Sanguíneas , Carcinoma de Ehrlich/metabolismo , Relação Dose-Resposta a Droga , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Óleos de Plantas/administração & dosagem , Ratos , Ratos WistarRESUMO
Psoralens are widely used for the treatment of hyperproliferative skin disease. In this work, we prepared nanoparticles (NP) containing a benzopsoralen (3-ethoxy carbonyl-2H-benzofuro[3,2-f]-1-benzopiran-2-one) by the solvent evaporation technique. We evaluated important NP parameters such as particle size, drug encapsulation efficiency, effect of the encapsulation process over the drug's photochemistry, zeta potential, external morphology, and in vitro release behavior. We also investigated the nanoparticle as a drug delivery system (DDS), as well as its target delivery to the action site, which is a very important parameter to increase the therapeutic use of psoralens and to reduce their side effects. The uptake of benzopsoralen-loaded PLGA nanoparticles by different kinds of cells found in rat peritoneal exudates was also studied. The photodamage promoted by irradiation with UV light revealed morphological characteristics of cell damage such as cytoplasmic vesiculation, mitochondrial damage, and swelling of both the granular endoplasmatic reticulum and nuclear membrane. This encapsulation method maintained the drug's properties and improved drug delivery to the target cell.
Assuntos
Líquido Ascítico/metabolismo , Fármacos Dermatológicos/metabolismo , Portadores de Fármacos , Furocumarinas/metabolismo , Ácido Láctico/química , Nanopartículas , Terapia PUVA , Fármacos Fotossensibilizantes/metabolismo , Ácido Poliglicólico/química , Polímeros/química , Animais , Líquido Ascítico/citologia , Líquido Ascítico/efeitos dos fármacos , Química Farmacêutica , Fármacos Dermatológicos/química , Fármacos Dermatológicos/farmacologia , Fármacos Dermatológicos/efeitos da radiação , Composição de Medicamentos , Endocitose , Furocumarinas/química , Furocumarinas/farmacologia , Furocumarinas/efeitos da radiação , Técnicas In Vitro , Cinética , Masculino , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/efeitos da radiação , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Wistar , Solubilidade , Propriedades de Superfície , Tecnologia Farmacêutica/métodos , Raios UltravioletaRESUMO
The immunomodulatory and anti-tumoral effects of an acidic heteropolysaccharide containing mainly galactose and arabinose (ARAGAL), isolated from the gum of the leguminous tree Anadenanthera colubrina (Angico branco) native to Brazil, were studied. It has been demonstrated that activation of mice peritoneal macrophages both in vivo and in vitro, increases phagocytic ability and anion superoxide production. In order to obtain further insights on the biological effects of ARAGAL, the capacity of eliciting peritoneal macrophages and tumor necrosis factor-alpha (TNF-alpha) production, and anti-tumoral effect against Sarcoma 180 (S-180), are now evaluated. Cell eliciting activity was observed in ARAGAL-treated animals in a dose dependent manner. Treatment of animals with 50, 100 or 200 mg/kg of ARAGAL increased peritoneal exudate cell (PEC) numbers by approximately 18, approximately 44 and approximately 88%, respectively. ARAGAL also increased 26-fold TNF-alpha production by peritoneal macrophages. Macrophages, treated in vitro for 18 h with ARAGAL, were able to kill Sarcoma 180 cells, as observed by their structures inside the macrophage cytoplasm. ARAGAL (100 mg/kg) showed anti-tumoral activity against S-180 in ascites or solid tumors, the tumoral inhibition being 63 and 38%, respectively. The results suggest a possible role as a BRM for ARAGAL.