RESUMEN
Allergic disease is caused by exposure to normally innocuous substances that activate mast cells. Mast cell-mediated allergic inflammation is closely related to a number of allergic disorders, such as anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. The discovery of drugs for treating allergic disease is an interesting subject and important to human health. The aim of the present study was to investigate the antiallergic and anti-inflammatory effects of the aqueous extract of Pogostemon cablin (Blanco) Benth (AEPC) (a member of the Labiatae family) using mast cells, and also to determine its possible mechanisms of action. An intraperitoneal injection of compound 48/80 or a serial injection of immunoglobulin E and antigen was used to induce anaphylaxis in mice. We found that AEPC inhibited compound 48/80induced systemic and immunoglobulin E-mediated cutaneous anaphylaxis in a dose-dependent manner. The release of histamine from mast cells was reduced by AEPC, and this suppressive effect was associated with the regulation of calcium influx. In addition, AEPC attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated expression of pro-inflammatory cytokines in mast cells. The inhibitory effects of AEPC on pro-inflammatory cytokines were dependent on the activation of nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK). AEPC blocked the PMACI-induced translocation of NF-κB into the nucleus by hindering the degradation of IκBα and the phosphorylation of p38 MAPK. Our results thus indicate that AEPC inhibits mast cellmediated allergic inflammation by suppressing mast cell degranulation and the expression of pro-inflammatory cytokines caused by reduced intracellular calcium levels and the activation of NF-κB and p38 MAPK.
Asunto(s)
Anafilaxia/tratamiento farmacológico , Antialérgicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Lamiaceae , Mastocitos/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Anafilaxia/inducido químicamente , Anafilaxia/inmunología , Animales , Antialérgicos/química , Antialérgicos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Calcio/inmunología , Degranulación de la Célula/efectos de los fármacos , Células Cultivadas , Citocinas/inmunología , Lamiaceae/química , Masculino , Ratones Endogámicos ICR , FN-kappa B/inmunología , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas Sprague-Dawley , p-Metoxi-N-metilfenetilamina , Proteínas Quinasas p38 Activadas por Mitógenos/inmunologíaRESUMEN
In this study, we investigated the effect of a water extract of the ripe fruits of Rubus coreanus Miq. (Rosaceae) (RFRC) on mast cell-mediated allergic inflammation and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. RFRC dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in mice. RFRC reduced the immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis. RFRC attenuated histamine release from rat peritoneal mast cells and human mast cells by the reduction of intracellular calcium. RFRC decreased the phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of RFRC on cytokine production was nuclear factor (NF)-κB- and mitogen-activated protein kinase (MAPK)-dependent. In addition, RFRC suppressed the activation of caspase-1. Our findings provide evidence that RFRC inhibits mast cell-derived allergic inflammatory reactions, and for the involvement of calcium, NF-κB, MAPKs and caspase-1 in these effects. Furthermore, in vivo and in vitro anti-allergic inflammatory effects of RFRC provide affirmative proof of a possible therapeutic application of this agent in allergic inflammatory diseases.
Asunto(s)
Anafilaxia/inmunología , Frutas/química , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Extractos Vegetales/farmacología , Rosaceae/química , Anafilaxia/inducido químicamente , Animales , Calcio/metabolismo , Caspasa 1/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Activación Enzimática/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Liberación de Histamina/efectos de los fármacos , Humanos , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , p-Metoxi-N-metilfenetilamina/efectos adversosRESUMEN
The effect of an aqueous extract of Phlomis umbrosa Turcz. (Labiatae) root (PUAE) on mast cell-dependent allergic reactions and inflammatory cytokine secretion were investigated. PUAE (0.01-1 g/kg) inhibited compound 48/80-induced systemic allergic reaction. When PUAE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. PUAE (0.1 and 1 g/kg) also significantly inhibited the local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. PUAE (0.001-1 mg/mL) dose-dependently inhibited the histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. PUAE (0.01-1 mg/mL) inhibited the secretion of interleukin (IL)-1beta in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells. PUAE (1 mg/mL) inhibited the gene expression and production of the main inflammatory cytokine, TNF-alpha, in HMC-1 cells. These results provide evidence that PUAE may be beneficial in the treatment of allergic diseases.
Asunto(s)
Citocinas/metabolismo , Hipersensibilidad/prevención & control , Mastocitos/efectos de los fármacos , Phlomis/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Animales , Western Blotting , Línea Celular , Citocinas/genética , Ensayo de Inmunoadsorción Enzimática , Expresión Génica/efectos de los fármacos , Liberación de Histamina/efectos de los fármacos , Humanos , Hipersensibilidad/inmunología , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Masculino , Mastocitos/metabolismo , Mastocitos/patología , Ratones , Ratones Endogámicos ICR , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/farmacologíaRESUMEN
In this study, we investigated the effect of aqueous extract of Prunella vulgaris (Labiatae; PVAE) on the mast cell-mediated allergy model. We found that PVAE (0.001-0.1 g/kg) dose dependently inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in mice. PVAE decreased the IgE-mediated local allergic reaction, passive cutaneous anaphylaxis. In addition, PVAE attenuated phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-alpha, IL-6, and IL-8 secretion in human mast cells. The inhibitory effect of PVAE on proinflammatory cytokines was nuclear factor-kappaB (NF-kappaB) dependent. PVAE suppressed PMA and A23187-induced NF-kappaB/DNA binding activity and NF-kappaB-dependent gene reporter assay. Our findings provide evidence that PVAE inhibits mast cell-derived immediate-type allergic reactions and involvement of proinflammatory cytokines and NF-kappaB in these effects.
Asunto(s)
Citocinas/metabolismo , Hipersensibilidad/metabolismo , Mastocitos/metabolismo , Extractos Vegetales/farmacología , Prunella/metabolismo , Animales , Histamina/metabolismo , Inflamación , Ionóforos/farmacología , Masculino , Mastocitos/inmunología , Ratones , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Acetato de Tetradecanoilforbol , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. The discovery of drugs for the treatment of immediate-type allergic diseases is a very important subject in human health. In this study, we investigated the effect of Artemisia iwayomogi (AIAE) on mast cell-mediated allergic reaction and inflammatory cytokine secretion. AIAE inhibited compound 48/80-induced systemic reactions in mice. AIAE decreased the passive cutaneous anaphylaxis (PCA) reaction activated by antidinitrophenyl (anti-DNP) IgE antibody. AIAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, AIAE attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 secretion in human mast cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.
Asunto(s)
Artemisia/química , Citocinas/metabolismo , Hipersensibilidad Inmediata/prevención & control , Extractos Vegetales/farmacología , Animales , Calcimicina/farmacología , Línea Celular Tumoral , Liberación de Histamina/efectos de los fármacos , Humanos , Hipersensibilidad Inmediata/inducido químicamente , Hipersensibilidad Inmediata/metabolismo , Inmunoglobulina E/administración & dosificación , Inmunoglobulina E/inmunología , Masculino , Mastocitos/citología , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Ratones , Ratones Endogámicos ICR , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Ratas , Ratas Sprague-Dawley , Acetato de Tetradecanoilforbol/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/administración & dosificación , p-Metoxi-N-metilfenetilamina/toxicidadRESUMEN
The immediate-type allergic reaction (anaphylaxis) is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. We investigated the effect of the gall of Rhus javanica (GRJ) on the model of the immediate-type allergic reaction, and studied its possible mechanisms. GRJ inhibited compound 48/80-induced systemic reactions in mice. GRJ attenuated immunoglobulin (Ig) E-mediated local allergic reactions. In addition, GRJ dose dependently decreased histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. The decreasing effect of GRJ on the histamine release was mediated by the modulation of cAMP and [Ca2+]i in mast cells. Furthermore, GRJ decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated TNF-alpha and IL-6 secretion in human mast cells. The inhibitory effect of GRJ on the pro-inflammatory cytokine was c-Jun N-terminal kinase and nuclear factor-kappaB dependent. Our findings provide evidence that GRJ inhibits mast cell-derived immediate-type allergic reactions, and suggest the possible mechanisms of action.