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1.
Inflammation ; 35(2): 746-57, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21830094

RESUMO

In the present study, we investigated the effects of Alpinia katsumadai H(AYATA) (Zingiberaceae) seed ethanolic extract (AKEE) and its three components on the production of inflammatory mediators and some potential underlying mechanisms in lipopolysaccharide (LPS)-induced inflammation RAW264.7 cells. The whole formula, AKEE, and three major component compounds were then evaluated for their effects on inflammation-related parameters using LPS-induced RAW264.7 cells. Production of namely nitric oxide (NO) and cytokine levels were measured by the Griess reagent and ELISA, respectively. To investigate the underlying mechanisms of anti-inflammatory activities of AKEE, protein expression of nitric oxide synthase (inducible nitric oxide synthase, iNOS), heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) were evaluated by western blot analysis. AKEE and the major group of compounds in AKEE (alpinetin, cardamonin, and pinocembrin) complement exert anti-inflammatory effects for NO and PGE(2) production. In addition, AKEE treatment significantly inhibited the LPS-induced production of interleukin-6 and tumor necrosis factor (TNF)-α, as well as the expression of iNOS. AKEE also induced HO-1 expression in RAW264.7 cells and inhibited the nuclear translocation of NF-κB by preventing degradation of the inhibitor kappa B-alpha. We also demonstrated that the effects of AKEE on TNF-α production were partially reversed by the HO-1 inhibitor tin protoporphyrin. These results indicate that AKEE and its major component may have anti-inflammatory activity via induction of HO-1 expression was partly responsible for the anti-inflammatory effects.


Assuntos
Alpinia , Heme Oxigenase-1/biossíntese , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Chalconas/farmacologia , Indução Enzimática , Flavanonas/farmacologia , Proteínas I-kappa B/metabolismo , Inflamação/enzimologia , Mediadores da Inflamação/metabolismo , Interleucina-6/biossíntese , Lipopolissacarídeos/imunologia , Metaloporfirinas/farmacologia , Camundongos , Inibidor de NF-kappaB alfa , NF-kappa B/biossíntese , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Prostaglandinas/biossíntese , Protoporfirinas/farmacologia , Sementes/metabolismo , Fator de Necrose Tumoral alfa/biossíntese
2.
Toxicol Int ; 18(2): 146-54, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21976821

RESUMO

Gumiganghwaltang (GGT) is a traditional oriental herbal prescription commonly used to treat colds and inflammatory diseases in Korea. This study reports the first evaluation of the oral toxicity and cytotoxicity effects of repeat doses of GGT. GGT was orally administered daily at doses of 0, 500, 1000, and 2000 mg/kg for 4 weeks. Analysis of body weight gain, mortality, clinical observations, urinalysis, blood biochemistry, hematology, organ weight, and histopathological data revealed no significant differences between the V.CONTROL and GGT-treated groups. In addition, we investigated the cytotoxicity of GGT against LNCaP, RBL-1, and BEAS-2B cell lines, and splenocytes. Based on the results, we conclude that GGT orally administered to rats is safe with no drug-related toxicity, even at the highest dose, in 4-week repeated dose studies. Thus, this concentration is considered the non-observable effect dose in rats.

3.
Int J Toxicol ; 30(5): 528-37, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21908652

RESUMO

This study evaluated the antiasthmatic effects of Gleditsia sinensis ethanolic extract (GSEE) and its underlying mechanisms, using an in vivo murine model of asthma. Female BALB/c mice were sensitized, challenged with ovalbumin, and then examined for asthmatic reactions. The results showed that GSEE exerted profound inhibitory effects on the accumulation of eosinophils in the airways and reduced the levels of interleukin (IL)-4 and IL-5 in bronchoalveolar lavage fluid (BALF) and immunoglobulin E (IgE) in BALF and plasma. Gleditsia sinensis ethanolic extract also suppressed the production of reactive oxygen species in BALF and inflammatory infiltration, in a dose-dependent manner, and it inhibited goblet-cell hyperplasia in lung tissue. Thus, GSEE shows antiasthmatic effects in a murine model of allergic asthma, which appeared to be mediated partially by the reduction of oxidative stress and airway inflammation. These results indicate that GSEE could be an effective novel therapeutic agent for the treatment of allergic asthma.


Assuntos
Antiasmáticos/farmacologia , Asma/induzido quimicamente , Asma/tratamento farmacológico , Gleditsia/química , Ovalbumina/toxicidade , Extratos Vegetais/farmacologia , Animais , Antiasmáticos/farmacocinética , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eosinófilos/metabolismo , Feminino , Células Caliciformes/efeitos dos fármacos , Imunoglobulina E/sangue , Inflamação/tratamento farmacológico , Interleucina-4/sangue , Interleucina-5/sangue , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/farmacocinética , Espécies Reativas de Oxigênio/antagonistas & inibidores
4.
Food Chem Toxicol ; 49(5): 1047-55, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21272610

RESUMO

In this study, we analyzed the anti-inflammatory effects of Angelica dahurica Bentham et Hooker ethanolic extract (ADEE) on RAW264.7 cells, to understand the mechanism underlying its observed effects. ADEE inhibited cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, leading to the suppression of COX-2-derived prostaglandin E(2) and iNOS-derived production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. These inhibitory effects of ADEE were accompanied by the reduced production of tumor necrosis factor α and interleukin (IL)-6. ADEE also inhibited nuclear factor κB (NFκB) translocation to the nucleus by interrupting inhibitor kappa Bα (IκBα) degradation. ADEE upregulated heme oxygenase 1 expression, and treatment with tin protoporphyrin IX (SnPP), a selective inhibitor of HO-1, reversed the LPS-induced generation of proinflammatory cytokines. ADEE also induced IL-4 and IL-5 expression in concanavalin-A-stimulated splenocytes. These results suggest that ADEE has anti-inflammatory activity, which acts via the suppression of the NF-κB pathway.


Assuntos
Angelica/química , Anti-Inflamatórios/farmacologia , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Extratos Vegetais/farmacologia , Animais , Western Blotting , Linhagem Celular , Sobrevivência Celular , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Proteínas I-kappa B/metabolismo , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Metaloporfirinas/metabolismo , Camundongos , Inibidor de NF-kappaB alfa , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Protoporfirinas/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
5.
Food Chem Toxicol ; 49(4): 829-37, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21146576

RESUMO

Asthma is a chronic immune inflammatory disease characterized by variable airflow obstruction. The present study was undertaken to assess the effects of an Angelica dahurica Bentham et Hooker ethanolic extract (AD) on airway inflammation in an ovalbumin (OVA)-induced airway inflammation model. Mice that received AD displayed significantly lower airway eosinophilia, cytokine levels, including interleukin (IL)-4, IL-5, and tumor necrosis factor (TNF)-alpha levels, mucus production and immunoglobulin (Ig)E, compared with OVA-induced mice. In our experiments, AD treatment reduced airway inflammation and suppressed oxidative stress in the OVA-induced asthma model, partly via induction of heme oxygenase (HO)-1. The effects of AD on OVA-induced HO-1 induction were partially reversed by the HO-1 inhibitor, tin protoporphyrin (SnPP). Our results clearly indicate that AD is a suppressor of airway allergic inflammation, and may thus be effectively used as an anti-inflammatory drug in the treatment of asthma.


Assuntos
Angelica/química , Antiasmáticos/uso terapêutico , Heme Oxigenase (Desciclizante)/metabolismo , Inflamação/prevenção & controle , Extratos Vegetais/uso terapêutico , Traqueia/patologia , Regulação para Cima/efeitos dos fármacos , Animais , Antiasmáticos/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Extratos Vegetais/farmacologia
6.
Int Immunopharmacol ; 10(11): 1374-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20727999

RESUMO

Asthma comprises a triad of reversible airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. Clinical and experimental findings have established eosinophilia as a sign of allergic disorders. In the present investigation, we evaluated the anti-asthmatic effects of schizandrin and its underlying mechanisms in an in vivo murine asthmatic model. To accomplish this, female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and examined for the following typical asthmatic reactions: increased numbers of eosinophils and other inflammatory cells in bronchoalveolar lavage fluid (BALF); production of Th1 cytokines (such as tumor necrosis factor (TNF)-α in BALF); production of Th2 cytokines (such as interleukin IL-4 and IL-5) in BALF; presence of total and OVA-specific immunoglobulins (Ig)E in serum; presence of oxidative stress; hyperplasia of goblet cells in the lung; and marked influx of inflammatory cells into the lung. Our results collectively show that schizandrin exerts profound inhibitory effects on accumulation of eosinophils into the airways and reduces the levels of IL-4, IL-5, IFN-γ, and TNF-α in BALF. Additionally, schizandrin suppresses the production of reactive oxygen species (ROS) in a dose-dependent manner, and inhibits goblet cell hyperplasia and inflammatory cell infiltration in lung tissue. Thus, schizandrin has anti-asthmatic effects, which seem to be partially mediated by reduction of oxidative stress and airway inflammation, in a murine allergic asthma model. These results indicate that schizandrin may be an effective novel therapeutic agent for the treatment of allergic asthma.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Ciclo-Octanos/uso terapêutico , Lignanas/uso terapêutico , Compostos Policíclicos/uso terapêutico , Animais , Asma/imunologia , Asma/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/biossíntese , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/imunologia , Células Caliciformes/patologia , Hiperplasia/tratamento farmacológico , Hiperplasia/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
7.
J Ethnopharmacol ; 130(1): 61-9, 2010 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-20420895

RESUMO

AIM OF THE STUDY: Traditionally, the stem and root bark of Ulmus davidiana var. japonica (Ulmaceae) are Korean herbal medicines used for anti-inflammatory and anticancer therapy. In this study, we investigated the protective effects of Ulmus davidiana var. japonica ethanolic extract (UD) in a murine asthma model. Furthermore, we determined whether heme oxygenase (HO)-1 is required for the protective activity of UD. MATERIALS AND METHODS: Airways of ovalbumin (OVA)-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. UD was applied 1h prior to OVA challenge. Mice were administered UD orally at doses of 100 and 200mg/kg once daily on days 18-23. Bronchoalveolar lavage fluid (BALF) was collected 48 h after the final OVA challenge. Levels of interleukin (IL)-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent assays (ELISAs). Lung tissue sections 4 microm in thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS (periodic acid shift reagent) staining, in conjunction with ELISA, immunohistochemistry and Western blot analyses for HO-1 protein expression. RESULTS AND CONCLUSION: Orally administered UD significantly inhibited the number of OVA-induced inflammatory cells and IgE production, along with reduced T-helper (Th)2 cytokine levels, such as IL-4 and IL-5, in BALF and lung tissue. In addition, UD induced a marked decrease in OVA-induced reactive oxygen species (ROS), inflammatory cell infiltration and mucus production in lung tissue. These effects were correlated with HO-1 mRNA and protein induction. Our results indicate that UD protects against OVA-induced airway inflammation, at least in part, via HO-1 upregulation.


Assuntos
Asma/tratamento farmacológico , Heme Oxigenase (Desciclizante)/metabolismo , Ovalbumina/farmacologia , Extratos Vegetais/uso terapêutico , Ulmus/química , Regulação para Cima/efeitos dos fármacos , Animais , Asma/induzido quimicamente , Asma/enzimologia , Sequência de Bases , Western Blotting , Líquido da Lavagem Broncoalveolar , Cromatografia Líquida de Alta Pressão , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Feminino , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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