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1.
J Agric Food Chem ; 65(37): 8128-8135, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28891650

RESUMO

The effects of asiaticoside (AS) on allergic responses mediated by mast cells were investigated. AS showed no obvious cytotoxicity on RPMCs (rat peritoneal mast cells). AS reduced the intracellular calcium in RPMCs and deprived the histamine release and degranulation. AS also decreased the generation of antigen-induced tumor necrosis factor α, interleukin (IL)-4, IL-8, and IL-1ß in RBL-2H3 cells sensitized by IgE. The suppression of AS on pro-inflammatory cytokines was related with the activation of the intracellular FcεRI and the inhibition of the nuclear factor-κB signaling pathway. In addition, AS disabled the phosphorylation of antigen-induced Syk, Lyn, Gab2, and PLCγ1, thus suppressing the downstream Akt phosphorylation and MAPKs pathways. It also increased HO-1 and Nrf2 expression time dependently. In summary, we demonstrate that AS suppresses the allergic inflammation mediated by mast cells and this effect might be mediated by FcεRI-dependent signaling pathways.


Assuntos
Hipersensibilidade/diagnóstico por imagem , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Triterpenos/administração & dosagem , Animais , Degranulação Celular/efeitos dos fármacos , Células Cultivadas , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Interleucina-8/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
2.
Mol Med Rep ; 13(1): 536-42, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26573554

RESUMO

Establishing therapeutic agents for the treatment of allergic diseases is an important focus of human health research. Sesamin, a lignan in sesame oil, exhibits a diverse range of pharmacological properties. However, to the best of our knowledge, the effect of sesamin on mast cell­mediated allergic responses has not yet been investigated. Thus, the aim of the present study was to investigate the effect of sesamin on mast cell­mediated allergic responses and the underlying mechanisms by which it produces this effect. In rats, oral administration of sesamin inhibited passive cutaneous anaphylaxis. Sesamin exposure attenuated immunoglobulin E­induced histamine release from rat peritoneal mast cells, which was indicated to be mediated by the modulation of intracellular calcium. In human mast cells, sesamin reduced the stimulatory effects of phorbol 12­myristate 13­acetate and calcium ionophore A23187 on the production and secretion of pro­inflammatory cytokines, including tumor necrosis factor­α and interleukin­6. The inhibitory effect of sesamin on pro­inflammatory cytokine production was dependent on nuclear factor κ­light­chain­enhancer of activated B cells (NF­κB) and p38 mitogen­activated protein kinase (MAPK). The present study demonstrates that sesamin inhibits mast cell­derived inflammatory allergic reactions by blocking histamine release, and pro­inflammatory cytokine production and secretion. In addition, the findings indicate that the effect of sesamin is mediated by its effect on p38 MAPK/NF­κB signaling. Furthermore, the in vivo and in vitro anti­allergic effects of sesamin reported in the present study suggest that it is a promising therapeutic agent for the treatment of inflammatory allergic diseases.


Assuntos
Dioxóis/farmacologia , Hipersensibilidade/imunologia , Lignanas/farmacologia , Mastócitos/imunologia , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , 2,4-Dinitrofenol/farmacologia , Animais , Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Ativação Enzimática/efeitos dos fármacos , Liberação de Histamina/efeitos dos fármacos , Humanos , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Masculino , Mastócitos/citologia , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Peritônio/citologia , Ratos Sprague-Dawley
3.
Mol Med Rep ; 12(5): 6946-54, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26502836

RESUMO

Allergic asthma is a chronic inflammatory disease that is regulated by coordination of T-helper type 2 cell cytokines and inflammatory signaling molecules. Ginsenoside Rh2 (G-Rh2) is an active component of ginseng with anti-inflammatory and anti-tumor effects. The aim of the present study was to determine the inhibitory effects of G-Rh2 on allergic airway inflammation in a murine model of asthma, in which mice develop the following pathophysiological features of asthma: Increased abundance of inflammatory cells; increased levels of interleukin-4 (IL-4), IL-5 and IL-13; decreased abundance of interferon gamma in the bronchoalveolar lavage fluid and lung tissue; increased total and ovalbumin (OVA)-specific immunoglobulin E (IgE) levels in the serum; increased airway hyperresponsiveness (AHR); and activation of nuclear factor kappa B (NF-κB) in lung tissue. In the asthmatic mice, administration of G-Rh2 markedly reduced peribronchiolar inflammation, recruitment of airway inflammatory cells, cytokine production, total and OVA-specific IgE levels and AHR. G-Rh2 administration inhibited NF-κB activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation induced by OVA inhalation. These results suggested that G-Rh2 attenuates allergic airway inflammation by regulating NF-κB activation and p38 MAPK phosphorylation. The present study identified the molecular mechanisms of action of G-Rh2, which supported the potential use of G-Rh2 to prevent and/or treat asthma and other airway inflammatory disorders.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Ginsenosídeos/uso terapêutico , Pulmão/efeitos dos fármacos , NF-kappa B/imunologia , Animais , Asma/sangue , Asma/patologia , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Interleucina-13/imunologia , Interleucina-4/imunologia , Interleucina-5/imunologia , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/sangue , Ovalbumina/imunologia
4.
Biochem Biophys Res Commun ; 427(3): 450-5, 2012 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-22842463

RESUMO

Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-κB) pathway. Because NF-κB activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-κB activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-κB activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.


Assuntos
Antioxidantes/uso terapêutico , Asma/tratamento farmacológico , Pneumonia/tratamento farmacológico , Silybum marianum , Silimarina/uso terapêutico , Animais , Asma/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia/patologia , Silibina , Células Th2/imunologia
5.
Int J Pharm ; 2010 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-20685383

RESUMO

To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol oleiqueCC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64mg/mL) and F2 (22.98mg/mL), compared to its intrinsic water solubility (1.51mg/mL). Nasal absorption of fexofenadine from these microemulsions was found to be fairly rapid. T(max) was observed within 5min after intranasal administration at 1.0mg/kg dose, and the absolute bioavailability (0-4h) was about 68% compared to the intravenous administration in rats. Our results suggested that these microemulsion formulations could be used as an effective intranasal dosage form for the rapid-onset delivery of fexofenadine.

6.
Int J Pharm ; 395(1-2): 309-16, 2010 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-20635476

RESUMO

To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol Oleique CC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64 mg/mL) and F2 (22.98 mg/mL), compared to its intrinsic water solubility (1.51 mg/mL). Nasal absorption of fexofenadine from these microemulsions was found to be fairly rapid. Tmax was observed within 5 min after intranasal administration at 1.0 mg/kg dose, and the absolute bioavailability (0-4 h) was about 68% compared to the intravenous administration in rats. Our results suggested that these microemulsion formulations could be used as an effective intranasal dosage form for the rapid-onset delivery of fexofenadine


Assuntos
Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Terfenadina/análogos & derivados , Administração Intranasal , Administração Oral , Animais , Disponibilidade Biológica , Química Farmacêutica , Composição de Medicamentos , Emulsões , Glicerídeos , Glicóis/química , Antagonistas não Sedativos dos Receptores H1 da Histamina/química , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacocinética , Injeções Intravenosas , Masculino , Mucosa Nasal/metabolismo , Óleos/química , Compostos Orgânicos/química , Tamanho da Partícula , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Solubilidade , Tensoativos/química , Tecnologia Farmacêutica/métodos , Terfenadina/administração & dosagem , Terfenadina/química , Terfenadina/farmacocinética , Viscosidade
7.
Allergol Int ; 58(1): 125-34, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19153539

RESUMO

BACKGROUND: Histamine is known to have immunoregulatory roles in allergic reactions through histamine receptor 1 (H1R), H2R, H3R and H4R. However, its role in goblet cell hyperplasia in the airways of asthma patients is yet to be clarified. OBJECTIVE: This study was designed to examine the role of histamine in goblet cell hyperplasia using histamine-deficient mice (Hdc-/- mice) with allergic airway inflammation. METHODS: Wild-type and Hdc-/- C57BL/6 mice were sensitized with ovalbumin (OVA). After a 2-week exposure to OVA, goblet cell hyperplasia was evaluated. Cell differentials and cytokines in BALF were analyzed. The mRNA levels of MUC5AC and Gob-5 gene were determined quantitatively. RESULTS: The number of eosinophils in BALF increased in both the sensitized wild-type mice and Hdc-/- mice with OVA inhalation. In addition, the numbers of alveolar macrophages and lymphocytes in BALF increased significantly in the sensitized Hdc-/- mice with OVA inhalation compared to the wild-type mice under the same conditions. The concentrations of Interleukin-4 (IL-4), IL-5, IL-13, Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and IL-2 in the BALF all increased significantly in both groups compared to those exposed to saline. In particular, the concentration of TNF-alpha in the Hdc-/- mice exposed to OVA was significantly higher than that in the wild-type mice under the same conditions. The mRNA levels of Gob-5 and MUC5AC, and the ratio of the goblet cells in the airway epithelium significantly increased in Hdc-/- mice exposed to OVA compared to wild-type mice. CONCLUSIONS: These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.


Assuntos
Asma/patologia , Células Caliciformes/patologia , Histamina/fisiologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Diferenciação Celular , Canais de Cloreto/genética , Citocinas/análise , Feminino , Histidina Descarboxilase/genética , Histidina Descarboxilase/fisiologia , Hiperplasia , Imunoglobulina E/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucina-5AC/genética , Mucoproteínas/genética
8.
J Pharmacol Sci ; 106(3): 354-60, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18360092

RESUMO

Although histamine is a central mediator in the immediate allergic reaction, its role in goblet cell hyperplasia in the airway of asthma is not completely understood. This study was designed to examine the role of histamine in goblet cell hyperplasia using histamine-deficient mice (Hdc(-/-) mice) with allergic airway inflammation. Wild-type and Hdc(-/-) C57BL/6 mice were sensitized with ovalbumin (OVA). After two-week exposure to OVA, goblet cell hyperplasia was evaluated. Cell differentials in BALF were analyzed. The mRNAs level of MUC5AC and Gob-5 gene were quantitatively determined. The number of eosinophils in BALF increased in both the wild-type mice and Hdc(-/-) mice; however, their ratio in Hdc(-/-) mice was significantly lower than that in the wild-type mice. The mRNA levels of Gob-5 and MUC5AC and the ratio of the goblet cells in the airway epithelium were significantly increased in Hdc(-/-) mice exposed to OVA compared to the wild-type mice under the same condition. These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.


Assuntos
Asma/patologia , Células Caliciformes/patologia , Histamina/fisiologia , Histidina Descarboxilase/fisiologia , Animais , Canais de Cloreto/genética , Citocinas/biossíntese , Feminino , Hiperplasia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucina-5AC , Mucinas/genética , Mucoproteínas/genética , Ovalbumina/imunologia
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