RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: A promising approach to treat a variety of diseases are considered as complementary and alternative herbal medicines. Prunus serrulata var. spontanea L. (Rosaceae) is used as herbal medicine to treat allergic diseases according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea. AIM OF THE STUDY: We prepared the aqueous extract of the bark of P. serrulata (AEBPS) and aimed to investigate the effects in mouse anaphylaxis models and various types of mast cells, including RBL-2H3, primary cultured peritoneal and bone marrow-derived mast cells. MATERIALS AND METHODS: We used ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models, in vivo. The control drug dexamethasone (10 mg/kg) was used to compare the effectiveness of AEBPS (1-100 mg/kg). In vitro, IgE-stimulated mast cells were used to confirm the role of AEBPS (1-100 µg/mL). For statistical analyses, p values less than 0.05 were considered to be significant. RESULTS: In ASA model, oral administration of AEBPS suppressed the hypothermia and increased level of serum histamine in a dose-dependent manner. AEBPS attenuated the serum IgE, OVA-specific IgE, and interleukin (IL)-4. Oral administration of AEBPS also blocked mast cell-dependent PCA. AEBPS suppressed degranulation of mast cells by reducing intracellular calcium level in mast cells. AEBPS inhibited tumor necrosis factor-α and IL-4 expression and secretion in a concentration-dependent manner through the reduction of nuclear factor-κB. CONCLUSIONS: On the basis of these findings, AEBPS could serve as a potential therapeutic target for the management of mast cell-mediated allergic inflammation and as a regulator of mast cell activation.
Asunto(s)
Anafilaxia/tratamiento farmacológico , Mastocitos/inmunología , Extractos Vegetales/farmacología , Prunus/química , Anafilaxia/inmunología , Animales , Relación Dosis-Respuesta a Droga , Histamina/sangre , Inmunoglobulina E/inmunología , Masculino , Medicina Tradicional Coreana , Ratones , Ratones Endogámicos ICR , Ovalbúmina/inmunología , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Anafilaxis Cutánea Pasiva/inmunología , Corteza de la Planta , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-DawleyRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Extracts from various parts of Ampelopsis brevipedunculata has been used as anti-inflammatory agents in Asian folk medicine. AIM OF THE STUDY: To demonstrate the medicinal effect of the A. brevipedunculata in skin inflammation, specifically atopic dermatitis (AD). MATERIALS AND METHODS: The effect of ethanol extract of A. brevipedunculata rhizomes (ABE) on AD was examined using an AD-like skin inflammation model induced by repeated exposure to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB). The mechanism study was performed using tumor necrosis factor (TNF)-α and interferon (IFN)-γ-activated human keratinocytes (HaCaT). Serum histamine and immunoglobulin levels were quantified using enzymatic kits, while the gene expression of cytokines and chemokines was analyzed using quantitative real time polymerase chain reaction. The expression of signaling molecules was detected using Western blot. RESULTS: Oral administration of ABE alleviated DFE/DNCB-induced ear thickening and clinical symptoms, as well as immune cell infiltration (mast cells and eosinophils) into the dermal layer. Serum Immunoglobulin (Ig) E, DFE-specific IgE, IgG2a, and histamine levels were decreased after the administration of ABE. ABE also inhibited CD4+IFN-γ+ and CD4+IL-4+ lymphocyte polarization in lymph nodes and expression of TNF-α, IFN-γ, IL-4, IL-13, and IL-31 in the ear tissue. In TNF-α/INF-γ-stimulated keratinocytes, ABE inhibited the gene expression of TNF-α, IL-6, IL-1ß, and CCL17. In addition, ABE decreased the nuclear localization of signal transducer and activator of transcription 1 and nuclear factor-κB, and the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. CONCLUSION: Collectively, our data demonstrate the pharmacological role and signaling mechanism of ABE in the regulation of skin allergic inflammation, which supports our suggestion that ABE could be developed as a potential therapeutic agent for the treatment of AD.
Asunto(s)
Ampelopsis , Antiinflamatorios/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antígenos Dermatofagoides/inmunología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocinas/inmunología , Dermatitis Atópica/sangre , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Dinitroclorobenceno , Etanol/química , Femenino , Histamina/sangre , Humanos , Inmunoglobulina E/sangre , Queratinocitos/efectos de los fármacos , Ratones Endogámicos BALB C , Extractos Vegetales/farmacología , Rizoma , Piel/efectos de los fármacos , Piel/inmunología , Piel/patología , Solventes/químicaRESUMEN
Atopic dermatitis (AD) is a common chronic inflammatory skin disorder afflicting from infancy to adults with itching, scratching, and lichenification. We aimed to investigate the effects of esculetin from Fraxinus rhynchophylla on atopic skin inflammation. For induction of atopic skin inflammation, we exposed the ears of female BALB/c mice to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB) for 4â¯weeks. Oral administration of esculetin reduced the symptoms of DFE/DNCB-induced atopic skin inflammation, which were evaluated based on ear swelling and number of scratch bouts. The immunoglobulin (Ig) E, IgG2a, and histamine levels in serum were decreased and inflammatory cell infiltration in skin tissue was reduced by the esculetin. It suppressed production of Th1, Th2 and Th17-related cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, IL-13, IL-31 and IL-17 in the ear tissue. Furthermore, we investigated the effects of esculetin on activated keratinocytes, which are representative cells used for studying the pathogenesis of acute and chronic atopic skin inflammation. As results, esculetin suppressed gene expression of Th1, Th2 and Th17 cytokines and the activation of nuclear factor-κB and signal transducer and activator of transcription 1 in TNF-α/IFN-γ-stimulated keratinocytes. Taken together, these results imply that esculetin attenuated atopic skin inflammation, suggesting that esculetin could be a potential therapeutic candidate for the treatment of AD.
Asunto(s)
Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Citocinas/antagonistas & inhibidores , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Umbeliferonas/farmacología , Umbeliferonas/uso terapéutico , Animales , Antígenos Dermatofagoides , Línea Celular , Citocinas/genética , Citocinas/inmunología , Dermatitis Alérgica por Contacto/inmunología , Dermatitis Alérgica por Contacto/metabolismo , Dinitroclorobenceno , Femenino , Fraxinus , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Factor de Transcripción STAT1/metabolismo , Piel/efectos de los fármacos , Piel/inmunologíaRESUMEN
Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. The present study investigated the effects of Amomum xanthioides extract (AXE) on ADlike skin inflammation using a Dermatophagoides farinae extract (DFE) and 2,4dinitrochlorobenzene (DNCB)induced mouse AD model. Hematoxylin and eosin staining results demonstrated that repeated DFE/DNCB exposure markedly increased the thickening of the dermis and epidermis, in addition to the infiltration of eosinophils and mast cells. However, oral administration of AXE reduced these histopathological alterations in a dosedependent manner. Elevated serum histamine, total and DFEspecific immunoglobulin E (IgE), and IgG2a were also decreased by treatment with AXE. In addition, reverse transcriptionquantitative polymerase chain reaction (RTqPCR) results demonstrated that the mRNA expression of tumor necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)4, IL13, IL31 and IL17A was reduced in ear skin following AXE administration in AD mice. Fluorescenceactivated cell sorting demonstrated that the population of CD4+/IL4+, CD4+/IFNγ+ and CD4+/IL17A+ cells in draining lymph nodes was also significantly decreased in AXEtreated mice compared with AD mice without AXE treatment. Furthermore, keratinocytes that were stimulated with TNFα and IFNγ exhibited increased gene expression of proinflammatory cytokines and chemokines, including TNFα, IL1ß, IL6, IL8, CC motif chemokine ligand (CCL)17 and CCL22, as determined by RTqPCR. However, upregulation of these genes was reduced by AXE pretreatment. Based on these results, we hypothesize that AXE may be useful in the treatment of allergic skin inflammation, particularly AD.
Asunto(s)
Amomum/química , Antiinflamatorios/farmacología , Dermatitis Atópica/inmunología , Extractos Vegetales/farmacología , Animales , Línea Celular , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Modelos Animales de Enfermedad , Histamina/sangre , Histamina/inmunología , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones , Piel/metabolismo , Piel/patologíaRESUMEN
CONTEXT: Diospyros kaki L. (Ebenaceae) fruit is widely distributed in Asia and is known to exert anti-inflammatory and antithrombotic effects. OBJECTIVE: We evaluated the inhibitory effect of aqueous extract of D. kaki calyx (AEDKC) on mast cell-mediated immediate-type hypersensitivity and underlying mechanism of action. MATERIALS AND METHODS: For in vivo, ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA, AEDKC (1-100 mg/kg) was orally administered 3 times during 14 days. In the PCA, AEDKC was orally treated 1 h before the antigen challenge. The control drug dexamethasone was used to compare the effectiveness of AEDKC. For in vitro, IgE-stimulated RBL-2H3 cells and primary cultured peritoneal mast cells were used to determine the role of AEDKC (0.01-1 mg/mL). RESULTS: Oral administration of AEDKC dose dependently suppressed rectal temperature decrease and increases in serum histamine, total IgE, OVA-specific IgE, and interleukin (IL)-4 in the ASA. In the PCA, AEDKC reduced Evans blue pigmentation. Compared to dexamethasone (10 mg/kg), AEDKC (100 mg/kg) showed similar inhibitory effects in vivo. AEDKC concentration dependently suppressed the release of histamine and ß-hexosaminidase through the reduction of intracellular calcium in mast cells. In addition, AEDKC decreased the expression and secretion of tumour necrosis factor-α and IL-4 by the reduction of nuclear factor-κB. The inhibitory potential of AEDKC (1 mg/mL) was similar with dexamethasone (10 µM) in vitro. CONCLUSIONS: We suggest that AEDKC may be a potential candidate for the treatment of mast cell-mediated allergic diseases.
Asunto(s)
Anafilaxia/metabolismo , Diospyros , Hipersensibilidad/metabolismo , Mastocitos/metabolismo , Extractos Vegetales/uso terapéutico , Anafilaxia/inducido químicamente , Anafilaxia/prevención & control , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Hipersensibilidad/prevención & control , Masculino , Mastocitos/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Ovalbúmina/inmunología , Ovalbúmina/toxicidad , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Atopic dermatitis (AD) is a common chronic inflammatory skin disease, affecting 10-20% of individuals worldwide. Therefore, the discovery of drugs for treating AD is an attractive subject and important to human health. Diospyros kaki and Diospyros kaki (D. kaki) folium exert beneficial effects on allergic inflammation. However, the effect of D. kaki calyx on AD remains elusive. The present study evaluated the effects of an aqueous extract of D. kaki calyx (AEDKC) on AD-like skin lesions using mouse and keratinocyte models. We used a mouse AD model by the repeated skin exposure of house dust mite extract [Dermatophagoides farinae extract (DFE)] and 2,4-dinitrochlorobenzene (DNCB) to the ears. In addition, to determine the underlying mechanism of its operation, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-activated keratinocytes (HaCaT) were used. Oral administration of AEDKC decreased AD-like skin lesions, as demonstrated by the reduced ear thickness, serum immunoglobulin E (IgE), DFE-specific IgE, IgG2a, histamine level and inflammatory cell infiltration. AEDKC inhibited the expression of pro-inflammatory cytokines and a chemokine via downregulation of nuclear factor-κB and signal transducer and activator of transcription 1 in HaCaT cells. On examination of the AD-related factors in vivo and in vitro, it was confirmed that AEDKC decreased AD-like skin lesions. Taken together, the results suggest that AEDKC is a potential drug candidate for the treatment of AD.
Asunto(s)
Antiinflamatorios/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Diospyros , Extractos Vegetales/uso terapéutico , Piel/efectos de los fármacos , Animales , Antiinflamatorios/química , Dermatitis Atópica/sangre , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/patología , Dinitroclorobenceno , Diospyros/química , Modelos Animales de Enfermedad , Femenino , Inmunoglobulina G/sangre , Queratinocitos/efectos de los fármacos , Queratinocitos/patología , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/química , Pyroglyphidae/química , Piel/patologíaRESUMEN
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
As the importance of allergic disorders such as atopic dermatitis and allergic asthma, research on potential drug candidates becomes more necessary. Mast cells play an important role as initiators of allergic responses through the release of histamine; therefore, they should be the target of pharmaceutical development for the management of allergic inflammation. In our previous study, anti-allergic effect of extracts of Amomum xanthioides was demonstrated. To further investigate improved candidates, 1,2,4,5-tetramethoxybenzene (TMB) was isolated from methanol extracts of A. xanthioides. TMB dose-dependently attenuated the degranulation of mast cells without cytotoxicity by inhibiting calcium influx. TMB decreased the expression of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-4 at both the transcriptional and translational levels. Increased expression of these cytokines was caused by translocation of nuclear factor-κB into the nucleus, and it was hindered by suppressing activation of IκB kinase complex. To confirm the effect of TMB in vivo, the ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and IgE-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA model, hypothermia was decreased by oral administration of TMB, which attenuated serum histamine, OVA-specific IgE, and IL-4 levels. Increased pigmentation of Evans blue was reduced by TMB in a dose-dependent manner in the PCA model. Our results suggest that TMB is a possible therapeutic candidate for allergic inflammatory diseases that acts through the inhibition of mast cell degranulation and expression of pro-inflammatory cytokines.
Asunto(s)
Anisoles/farmacología , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Amomum , Animales , Degranulación de la Célula/efectos de los fármacos , Citocinas/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Hipersensibilidad , Quinasa I-kappa B/biosíntesis , Mediadores de Inflamación/antagonistas & inhibidores , Masculino , Mastocitos/efectos de los fármacos , Ratones , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Salvia plebeia R. Br. has been used to treat a variety of inflammatory diseases and as an antioxidant in many countries, including Korea and China. In this study, we investigated the effects of S. plebeia extract (SPE) on inflammatory arthritis and the underlying mechanisms of action. We used a collagen-induced arthritis (CIA) mouse model. TNF-α-stimulated rheumatoid arthritis (RA) synovial fibroblasts were used to elucidate the underlying mechanisms of action. Oral administration of SPE improved the clinical arthritis score, footpad thickness, and histologic changes, as well as serum IgG1 and IgG2a levels. SPE administration inhibited Th1/Th2/Th17 phenotype CD4(+) T lymphocyte expansion in inguinal lymph node and expression of inflammatory mediators such as cytokines, MMP-1, and MMP-3 in the ankle joint tissue. SPE significantly suppressed the expression of cytokines and MMP-1 by down-regulating NF-κB, Akt, and mitogen-activated protein kinases in RA synovial fibroblasts. Taken together, these results indicate that SPE is therapeutically efficacious against chronic inflammatory arthritis, suggesting that SPE is a candidate for treating RA.
Asunto(s)
Antiinflamatorios/farmacología , Artritis Experimental/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Fibroblastos/efectos de los fármacos , Salvia/química , Animales , Artritis Reumatoide/tratamiento farmacológico , Linfocitos T CD4-Positivos/inmunología , Canfanos , Células Cultivadas , Citocinas/inmunología , Humanos , Inmunoglobulina G/sangre , Masculino , Metaloproteinasas de la Matriz/inmunología , Ratones , Ratones Endogámicos BALB C , Panax notoginseng , Componentes Aéreos de las Plantas/química , Salvia miltiorrhizaRESUMEN
Salvia plebeia R. Br. (Lamiaceae) has been used for folk medicines in Asian countries, including Korea and China, to treat skin inflammatory diseases and asthma. In this study, we investigated the effects of S. plebeia extract (SPE) on atopic dermatitis (AD)-like skin lesions and defined underlying mechanisms of action. We established an AD model in BALB/c mice by repeated local exposure of house dust mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB) to the ears. Repeated alternative treatment of DFE/DNCB caused AD-like skin lesions. The oral administration of SPE decreased AD symptoms based on ear thickness and histopathological analysis, in addition to serum IgE and IgG2a levels. SPE suppressed mast cell infiltration into the ear and serum histamine level. SPE inhibited Th1/Th2/Th17 phenotype CD4(+) T lymphocytes expansion in the lymph node and the expression of Th1/Th2/Th17 cytokines in the ear tissue. To define the underlying mechanisms of action, the tumor necrosis factor (TNF)-α and interferon (IFN)-γ activated human keratinocytes (HaCaT) model was used. SPE significantly suppressed the expression of cytokines and chemokines through the down-regulation of mitogen-activated protein kinases, nuclear factor-κB, and STAT1 in HaCaT cells. Taken together, our results suggest that SPE might be a candidate for the treatment of AD.
Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Fitoterapia , Salvia , Administración Oral , Animales , Canfanos , Células Cultivadas , Citocinas/metabolismo , Dermatitis Atópica/patología , Modelos Animales de Enfermedad , Oído Externo , Femenino , Histamina/sangre , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Mediadores de Inflamación/metabolismo , Queratinocitos/inmunología , Queratinocitos/metabolismo , Ganglios Linfáticos/inmunología , Mastocitos/inmunología , Ratones Endogámicos BALB C , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Panax notoginseng , Salvia miltiorrhiza , Piel/inmunología , Piel/patología , Linfocitos T/inmunologíaRESUMEN
The antiallergic effects of traditional medicines have long been studied. Traditional Korean medicine, Citrus sunki and bamboo salt, has been used for the treatment of allergic diseases in Korea. K-ALL, composed of Citrus sunki and bamboo salt, is a newly prepared prescription for allergic patients. To develop the new antiallergic agent, we examined the effects of K-ALL through in vivo and in vitro models. K-ALL and naringin (an active compound of K-ALL) significantly inhibited histamine release from rat peritoneal mast cells. This inhibitory effect of K-ALL on histamine release was higher than effects from other known histamine inhibitors such as bamboo salt, Citrus sunki or disodium cromoglycate. K-ALL significantly inhibited systemic anaphylactic shock induced by the compound 48/80 and passive cutaneous anaphylaxis induced by the IgE. K-ALL also inhibited production and mRNA expression of inflammatory cytokines induced by phorbol 12-myristate 13-acetate and the calcium ionophore A23187 on HMC-1 cells (a human mast cell line). In the ovalbumin-induced allergic rhinitis animal model, rub scores, histamine, IgE, inflammatory cytokines and inflammatory cell counts were all reduced by the oral or nasal administration of K-ALL (pre and posttreatment). These results indicate the great potential of K-ALL as an active immune modulator for the treatment of mast cell-mediated allergic diseases.
Asunto(s)
Anafilaxia/tratamiento farmacológico , Citrus/química , Mastocitos/metabolismo , Medicina Tradicional Coreana , Extractos Vegetales/farmacología , Rinitis Alérgica Perenne/tratamiento farmacológico , Administración Intranasal , Administración Oral , Anafilaxia/metabolismo , Anafilaxia/patología , Animales , Calcimicina/farmacología , Ionóforos de Calcio/farmacología , Carcinógenos/farmacología , Línea Celular , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Mastocitos/patología , Ratones , Ratones Endogámicos ICR , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Rinitis Alérgica , Rinitis Alérgica Perenne/metabolismo , Rinitis Alérgica Perenne/patología , Acetato de Tetradecanoilforbol/farmacocinéticaRESUMEN
Diospyros kaki (D. kaki) has been cultivated throughout Eastern Asia for hundreds of years. D. kaki contains various biological active compounds, such as amino acids, carotenoids, ï¬avonoids, tannins, catechins and vitamin A. Previous studies have shown that D. kaki has beneficial effects on homeostasis, constipation, hypertension, atherosclerosis and allergic dermatitis and is a good source of antioxidants, polyphenols and dietary ï¬ber. However, the anti-allergic and anti-inflammatory effects of D. kaki have not yet been elucidated. This study aimed to investigate the protective effects of the aqueous extract of Diospyros kaki (AEDK) on mast cell-mediated allergic inflammation and to determine its possible mechanisms of action by using in vitro and in vivo mast cell-based models. The cAMP and intracellular calcium levels were measured to clarify the mechanisms by which AEDK inhibits the release of histamine from mast cells. AEDK inhibited the release of histamine and ß-hexosaminidase from mast cells by modulating cAMP and intracellular calcium levels. We also measured the expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. AEDK decreased gene expression and the secretion of the pro-inflammatory cytokines, TNF-α and IL-1ß by inhibiting nuclear factor-κB. In addition, AEDK inhibited systemic and cutaneous allergic reaction. The inhibitory effects of AEDK on allergic reaction and the release of histamine were found to be similar to those of disodium cromoglycate, a known anti-allergic drug. To isolate the active component of AEDK, activity-guided fractionation was performed, based on the inhibitory effects on systemic anaphylaxis. Catechin was identified as an active compound. The present findings provide evidence that AEDK inhibits allergic inflammation and suggest the therapeutic application of AEDK in allergic inflammatory disorders.
Asunto(s)
Calcio/metabolismo , Diospyros/química , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Antiasmáticos/farmacología , Línea Celular , Cromolin Sódico/farmacología , Modelos Animales de Enfermedad , Liberación de Histamina/efectos de los fármacos , Humanos , Hipersensibilidad/tratamiento farmacológico , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Ratones , Ratones Endogámicos ICR , FN-kappa B/antagonistas & inhibidores , FN-kappa B/genética , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Allergic inflammatory diseases such as food allergy, asthma, sinusitis, and atopic dermatitis are increasing worldwide. In this study, we investigated the effects of aqueous extract of Mosla chinensis Max. (AMC) on mast cell-mediated allergic inflammation and studied the possible mechanism of this action. AMC inhibited compound 48/80-induced systemic and immunoglobulin E (IgE)-mediated local anaphylaxis. AMC reduced intracellular calcium levels and downstream histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. In addition, AMC decreased gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 in human mast cells. The inhibitory effect of AMC on cytokine expression was nuclear factor (NF)-κB dependent. Our results indicate that AMC inhibits mast cell-mediated allergic inflammatory reaction by suppressing histamine release and expression of proinflammatory cytokines and the involvement of calcium and NF-κB in these effects. AMC might be a possible therapeutic candidate for allergic inflammatory disorders.
Asunto(s)
Hipersensibilidad/prevención & control , Inflamación/prevención & control , Lamiaceae/química , Mastocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Western Blotting , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Liberación de Histamina/efectos de los fármacos , Hipersensibilidad/inmunología , Hipersensibilidad/metabolismo , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Masculino , Mastocitos/metabolismo , Ratones , Ratones Endogámicos ICR , Ratas , Ratas Sprague-DawleyRESUMEN
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
Mast cell-mediated allergic reaction is involved in many diseases such as asthma and allergic rhinitis. Therefore, discovery of drugs for the prevention or treatment of allergic disease is an important topic in human health. In this study, we evaluated the effects of water extract of Elsholtzia ciliata (Thunb.) Hyland (Labiatae) (WEEC) on mast cell-mediated allergic inflammation and studied the possible mechanisms of action. WEEC inhibited compound 48/80-induced systemic and immunoglobulin E-mediated local anaphylaxis, and serum histamine release in mice. WEEC reduced intracellular calcium levels and downstream histamine release from human mast cells (HMC-1) activated with phorbol 12-myristate 13-acetate and calcium ionophore A23187. In addition, WEEC decreased gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1ß and IL-6 in HMC-1. The inhibitory effect of WEEC on cytokine expression was nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) dependent. Our results indicate that WEEC inhibits mast cell-mediated allergic inflammatory reactions by suppressing histamine release and proinflammatory cytokine expression, and involvement of calcium, NF-κB and p38 MAPK in these effects.
Asunto(s)
Calcio/fisiología , Hipersensibilidad/tratamiento farmacológico , Lamiaceae , Mastocitos/efectos de los fármacos , FN-kappa B/fisiología , Extractos Vegetales/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología , Animales , Calcio/sangre , Liberación de Histamina/efectos de los fármacos , Hipersensibilidad/fisiopatología , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Masculino , Mastocitos/fisiología , Ratones , Ratones Endogámicos ICR , FN-kappa B/efectos de los fármacos , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , p-Metoxi-N-metilfenetilamina/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacosRESUMEN
The leaves of Eriobotrya japonica Lindl. have been widely used as a traditional medicine for the treatment of many diseases including gastroenteric disorders, diabetes mellitus, chronic bronchitis and asthma. In the present study, the anti-metastatic action of the EtOAc fraction of the leaves of E. japonica (LEJ) was investigated. LEJ showed potent inhibitory effects on MMP-2 and MMP-9 activities and expressions via down-regulation of NF-κB translocation to the nucleus in B16F10 cells. In addition, the cell migration and invasion were down-regulated by LEJ. LEJ also significantly suppressed lung metastasis in vivo. Moreover, we isolated the compounds ursolic acid and 2α-hydroxyursolic acid from LEJ and both compounds also significantly suppressed MMP-2 and MMP-9 activities, indicating that they are the active components of LEJ. The present results demonstrate that LEJ may be used as valuable antimetastatic agent for the treatment of cancer metastasis.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Eriobotrya/química , Extractos Vegetales/farmacología , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/uso terapéutico , Movimiento Celular/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Núcleo Celular/enzimología , Proliferación Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , Metaloproteinasa 9 de la Matriz , Inhibidores de la Metaloproteinasa de la Matriz , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/secundario , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , FN-kappa B/metabolismo , Invasividad Neoplásica , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Transporte de Proteínas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Mast cell-mediated allergic symptoms are involved in many diseases, such as asthma and sinusitis. In this study, we investigated the effect of ethanol extract of fruits of Prunus persica (L) Batsch (FPP) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. FPP dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated local allergic reactions. Histamine releasing from mast cells was reduced by FPP, which was mediated by modulation of intracellular calcium. In addition, FPP attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of FPP on pro-inflammatory cytokines was nuclear factor (NF)-kappaB dependent. Our findings provide evidence that FPP inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-kappaB in these effects.
Asunto(s)
Antialérgicos/farmacología , Antiinflamatorios/farmacología , Señalización del Calcio/efectos de los fármacos , FN-kappa B/metabolismo , Prunus/química , Anafilaxia/inmunología , Anafilaxia/prevención & control , Animales , Western Blotting , Calcio/metabolismo , Citocinas/biosíntesis , Liberación de Histamina/efectos de los fármacos , Indicadores y Reactivos , Interleucina-8/metabolismo , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Ratones , Ratones Endogámicos ICR , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Extractos Vegetales/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/farmacologíaRESUMEN
Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In this study, we investigated the effect of the water extract of Clinopodium gracile Matsum var. multicaule (WECG) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. WECG inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated cutaneous anaphylaxis in a dose-dependent manner. WECG dose-dependently reduced histamine release from rat peritoneal mast cells and human mast cells. The inhibitory effect of WECG on histamine release was mediated by the modulation of intracellular calcium. In addition, WECG attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 in human mast cells. The inhibitory effect of WECG on these proinflammatory cytokines was nuclear factor-kappaB (NF-kappaB) dependent. Our findings provide evidence that WECG inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-kappaB in these effects.
Asunto(s)
Calcio/metabolismo , Hipersensibilidad/complicaciones , Hipersensibilidad/tratamiento farmacológico , Lamiaceae/química , Mastocitos/inmunología , FN-kappa B/metabolismo , Extractos Vegetales/uso terapéutico , Anafilaxia/inducido químicamente , Anafilaxia/tratamiento farmacológico , Animales , Citocinas/genética , Citocinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Liberación de Histamina/efectos de los fármacos , Liberación de Histamina/inmunología , Hipersensibilidad/metabolismo , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Masculino , Mastocitos/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Anafilaxis Cutánea Pasiva/inmunología , Fitoterapia , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , p-Metoxi-N-metilfenetilaminaRESUMEN
Three compounds were isolated from the ethyl acetate soluble fraction of the methanolic extract of the leaves of Catalpa ovata (Bignoniaceae) through repeated column chromatography. We investigated the effects of these compounds on T cell-mediated responses for tumor surveillance and proliferation in U937, HL60, and Molt-4 leukemia cells. Compounds 1-3 inhibited proliferation of those cells in a dose-dependent manner. Compound 3 showed mild effect in Molt-4 cell cytotoxicity. Compound 3 enhanced gene expressions of p53 and IL-4, but decreased IL-2 and IFN-Gamma genes in Molt-4 cell. Our findings indicate that compound 3 may enhance T cell-mediated immune responses and anticancer properties.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Bignoniaceae/química , Inmunidad Celular/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Linfocitos T/efectos de los fármacos , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Apoptosis/genética , Apoptosis/inmunología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/biosíntesis , Citocinas/inmunología , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Expresión Génica/efectos de los fármacos , Células HeLa , Humanos , Inmunidad Celular/inmunología , Medicina Tradicional Coreana , Estructura Molecular , Hojas de la Planta/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/inmunología , Células U937RESUMEN
Mast cell-mediated allergic inflammation is involved in many diseases such as asthma and sinusitis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 with immune regulatory properties. In the present study, we investigate the effect an unspecified aqueous extract from leaves of Eriobotrya japonica Lindl. (Rosaceae) (LEJL) on the expression of pro-inflammatory cytokines and its possible mechanisms of action in human mast cells (HMC-1). LEJL dose-dependently inhibited phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 (PMACI)-induced gene expression and secretion of TNF-alpha, IL-6, and IL-8. LEJL attenuated PMACI-induced activation of nuclear factor (NF)-kappaB, and specifically blocked activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) but not that of c-jun N-terminal kinase. The inhibitory effect of LEJL on the pro-inflammatory cytokines was likely NF-kappaB, p38 MAPK, and ERK dependent. Our in vitro studies provide evidence that LEJL might contribute to the treatment of mast cell-derived allergic inflammatory diseases.