RESUMO
Selenium-rich tea polysaccharides (Se-TPS) were extracted via high hydrostatic pressure technology with a pressure of 400 MPa (200-500 MPa) for 10 min (3-20 min) at a material-to-solvent ratio of 1:40 (1:20-1:50). Subsequently, Se-TPS1-4 were isolated and purified, with Se-TPS3-4 as the main components. A spectral analysis proved that Se, which has antioxidant activity, existed. An in vitro study found that among Se-TPS, Se-TPS3-4 attenuated the release of ß-hexosaminidase, histamine, and interleukin (IL)-4. Furthermore, in vivo experiments revealed that treatment with Se-TPS downregulated IL-4 levels and upregulated TGF-ß and interferon-γ levels to improve imbalanced Th1/Th2 immunity in tropomyosin-sensitized mice. Moreover, Se-TPS promoted Lactobacillus and norank_f_Muribaculaceaek growth and upregulated metabolites such as genipin and coniferyl alcohol. Overall, these results showed the strong anti-allergy potential of Se-TPS by regulating mast cell-mediated allergic inflammatory responses and microbiota regulation, highlighting the potential of Se-TPS as a novel therapeutic agent to regulate allergy-associated metabolic disorders.
Assuntos
Microbioma Gastrointestinal , Pressão Hidrostática , Polissacarídeos , Chá , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Camundongos , Chá/química , Mastócitos/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Antialérgicos/farmacologia , Antialérgicos/química , Antialérgicos/isolamento & purificação , beta-N-Acetil-Hexosaminidases/metabolismo , Citocinas/metabolismo , Masculino , Tropomiosina/metabolismo , Tropomiosina/imunologiaRESUMO
In this study, we investigated the anti-allergic effects of 3,4-dihydroxybenzaldehyde (DHB) isolated from the marine red alga, Polysiphonia morrowii, in mouse bone-marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in anti-dinitrophenyl (DNP) immunoglobulin E (IgE)-sensitized mice. DHB inhibited IgE/bovine serum albumin (BSA)-induced BMCMCs degranulation by reducing the release of ß-hexosaminidase without inducing cytotoxicity. Further, DHB dose-dependently decreased the IgE binding and high-affinity IgE receptor (FcεRI) expression and FcεRI-IgE binding on the surface of BMCMCs. Moreover, DHB suppressed the secretion and/or the expression of the allergic cytokines, interleukin (IL)-4, IL-5, IL-6, IL-13, and tumor necrosis factor (TNF)-α, and the chemokine, thymus activation-regulated chemokine (TARC), by regulating the phosphorylation of IκBα and the translocation of cytoplasmic NF-κB into the nucleus. Furthermore, DHB attenuated the passive cutaneous anaphylactic (PCA) reaction reducing the exuded Evans blue amount in the mouse ear stimulated by IgE/BSA. These results suggest that DHB is a potential therapeutic candidate for the prevention and treatment of type I allergic disorders.
Assuntos
Antialérgicos/farmacologia , Benzaldeídos/farmacologia , Catecóis/farmacologia , Mastócitos/efeitos dos fármacos , Rodófitas/metabolismo , Animais , Antialérgicos/administração & dosagem , Antialérgicos/isolamento & purificação , Benzaldeídos/administração & dosagem , Benzaldeídos/isolamento & purificação , Catecóis/administração & dosagem , Catecóis/isolamento & purificação , Células Cultivadas , Citocinas/imunologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Imunoglobulina E/imunologia , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Anafilaxia Cutânea Passiva/imunologia , Soroalbumina Bovina/imunologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Flos Magnoliae (the dried flower buds of Magnolia biondii Pamp, FM) is a known herbal traditional medicine used for the symptomatic relief of nasal congestion and rhinorrhea caused by rhinitis and sinusitis. Magnolol, a neolignan from the magnolia family, is a secondary metabolite known to have anti-allergic and anti-inflammatory effects. However, the underlying mechanisms and therapeutic effect of magnolol in the treatment of allergic rhinitis (AR) remain elusive. AIMS OF THE STUDY: Anoctamin 1 (ANO1), a calcium-activated anion channel, mediates mucus and electrolyte secretion in nasal airway epithelial cells, whereas calcium release-activated calcium channel protein 1 (ORAI1) participates in the activation of T-lymphocytes and mast cells. The aim of our study is to understand the mechanisms of action of magnolol against AR, i.e., whether it acts through the modulation of ANO1 and ORAI1 channels that are expressed in nasal epithelial cells and T-lymphocytes, respectively. MATERIALS AND METHODS: Whole-cell patch clamp was used to record the activity of ORAI1 and ANO1 ion channels in ORAI1 or ANO1 overexpressed HEK293T cells, while the Ussing chamber apparatus was used to measure electrolyte transport via the epithelium, in Calu-3 cells cultured in an air-liquid interface. Additionally, calcium imaging of Jurkat T-lymphocytes was used to assess changes in the intracellular calcium concentration. Magnolol toxicity was assessed using the CCK-8 assay, and its effect on T-lymphocyte proliferation was measured by labeling human primary T-lymphocytes with carboxyfluorescein succinimidyl ester. Finally, OVA-induced Balb/c mice were employed to evaluate the effect of magnolol on nasal symptoms, as well as cytokine and eosinophil infiltration in AR. RESULTS: Magnolol inhibits ORAI1 and ANO1 channels in a concentration-dependent manner. Magnolol (30 µM) inhibits anti-CD3 induced cellular proliferation and production of IL-2 via ORAI1 channels in T-lymphocytes. Further, ATP-induced electrolyte transport mediated by ANO1 channels is significantly inhibited by magnolol in IL-4 sensitized Calu-3 cells. Notably, 300 µM magnolol significantly attenuates cytokine and eosinophil infiltration, thus alleviating AR symptoms in mice OVA-induced AR. CONCLUSION: Magnolol may be a promising therapeutic agent for the treatment and prevention of AR.
Assuntos
Antialérgicos/farmacologia , Compostos de Bifenilo/farmacologia , Lignanas/farmacologia , Magnolia/química , Rinite Alérgica/tratamento farmacológico , Animais , Anoctamina-1/antagonistas & inibidores , Antialérgicos/administração & dosagem , Antialérgicos/isolamento & purificação , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/isolamento & purificação , Linhagem Celular Tumoral , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Flores , Células HEK293 , Humanos , Lignanas/administração & dosagem , Lignanas/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/antagonistas & inibidores , Proteína ORAI1/antagonistas & inibidores , Ovalbumina , Técnicas de Patch-ClampRESUMO
Lotus seed pod (LSP) has been used as traditional herbal cuisine to modulate immunity. From the AcOEt-soluble extract of LSP, one new aporphine alkaloid, N-[2-(2H-phenanthro[3,4-d][1,3]dioxol-5-yl)ethyl]acetamide (nelunucine A, 1) was obtained along with 19 known ones. Their structures were established by detailed analysis of the 1D-, 2D-NMR, and HR-ESI-MS data. N-Nornuciferine (9) and lirinidine (10) showed potent inâ vitro anti-food allergic activity with IC50 values of 40.0 and 55.4â µM, respectively, compared to 91.4â µM for loratadine, the positive control.
Assuntos
Alcaloides/uso terapêutico , Antialérgicos/uso terapêutico , Hipersensibilidade Alimentar/tratamento farmacológico , Lotus/química , Sementes/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Linhagem Celular , Estrutura Molecular , RatosRESUMO
Allergic rhinitis (AR) is a common chronic respiratory disease. Asarum heterotropoides (AH) is predicted to be a treatment for allergic diseases, but its therapeutic effect is unclear. We aimed to determine the anti-allergic effects of AH in mice with ovalbumin (OVA)-induced AR. OVA-induced AR mouse model was constructed, and AH was orally administered for a week; next, nasal clinical symptoms were evaluated. The levels of serum histamine, OVA-specific IgE, and IL-13 were measured by ELISA. Inflammatory cells, including leukocytes, neutrophils, eosinophils, and macrophages were counted in the nasal lavage fluid (NALF). Histopathological examinations of the nasal tissues were performed using H&E, Giemsa, and PAS staining. The production of periostin and eotaxin-3 from AH-treated human nasal epithelial cells (HNEpCs) in vitro, was measured using ELISA. Oral administration of AH alleviated allergic symptoms in mice with AR; significantly decreased levels of allergic mediators, such as serum histamine and OVA-specific IgE. The decrease in allergic symptoms positively correlated with the decrease in serum allergic mediators. The NALF of AH-treated AR mice demonstrated lower number of eosinophils. AH demonstrated a capacity to reduce the infiltration of mast cells, eosinophils, and goblet cells, thereby resulting in thinner nasal tissues. Moreover, treatment of HNEpCs with AH demonstrated suppressed production of periostin and eotaxin-3. AH exerts a therapeutic effect in modulating AR through multi-target and multi-function influence on regulating B cells, mast cells, eosinophils, goblet cells, and epithelial cells.
Assuntos
Antialérgicos/uso terapêutico , Asarum , Ovalbumina/toxicidade , Extratos Vegetais/uso terapêutico , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/tratamento farmacológico , Animais , Antialérgicos/isolamento & purificação , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Rinite Alérgica/imunologiaRESUMO
Ten new (1-10) and 26 known (11-36) compounds were isolated from Penicillium griseofulvum MCCC 3A00225, a deep sea-derived fungus. The structures of the new compounds were determined by detailed analysis of the NMR and HRESIMS spectroscopic data. The absolute configurations were established by X-ray crystallography, Marfey's method, and the ICD method. All isolates were tested for in vitro anti-food allergic bioactivities in immunoglobulin (Ig) E-mediated rat basophilic leukemia (RBL)-2H3 cells. Compound 13 significantly decreased the degranulation release with an IC50 value of 60.3 µM, compared to that of 91.6 µM of the positive control, loratadine.
Assuntos
Antialérgicos/farmacologia , Basófilos/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Hipersensibilidade Alimentar/tratamento farmacológico , Penicillium/metabolismo , Animais , Antialérgicos/isolamento & purificação , Basófilos/imunologia , Linhagem Celular Tumoral , Hipersensibilidade Alimentar/imunologia , Sedimentos Geológicos/microbiologia , Imunoglobulina E/imunologia , Estrutura Molecular , Ratos , Relação Estrutura-AtividadeRESUMO
Piper crocatum Ruiz & Pav. (P. crocatum), a traditional medicinal plant, has been shown to possess various pharmacological activities, including anticancer activity, antioxidant activity, antibacterial activity, anti-hyperglycemic activity, anti-allergic inflammatory activity and others. To identify the potential anti-allergic inflammatory effective constituents of P. crocatum, 13 single compounds were isolated from the methanol extract of P. crocatum leaves, and their structures were identified by contrasting their NMR spectroscopic data and previously published papers. First, the anti-allergic inflammatory activities of these single compounds were examined by accessing immune function related biomarkers such as nitric oxide (NO) and ß-hexosaminidase. We found that the methanol extract and catechaldehyde (compound 1) potently suppressed NO production. Additionally, Western blot analysis showed that P. crocatum methanol extract and compound 1 suppressed the production of NO by reducing inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these observations, P. crocatum methanol extract and compound 1 remarkably decreased ß-hexosaminidase release from RBL-2H3 cells stimulated with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA)-specific immunoglobulin E (IgE) antibodies. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicated that P. crocatum methanol extract and compound 1 exhibited no cytotoxicity to RAW264.7 and RBL-2H3 cells. Based on these findings, compound 1 is suggested as an active anti-allergic inflammatory component of P. crocatum.
Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Piper/química , Extratos Vegetais/farmacologia , Animais , Antialérgicos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Metanol/química , Camundongos , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Células RAW 264.7 , RatosRESUMO
Cordyceps militaris has been widely studied for its various pharmacological activities such as antitumor, anti-inï¬ammation, and immune regulation. The binding of an allergen to IgE-sensitized mast cells in nasal mucosa triggers allergic rhinitis. We found that oral administration of 300 mg/kg of the ethanol extract prepared from silkworm pupa-cultivated Cordyceps militaris fruiting bodies signiï¬cantly alleviated the symptoms of ovalbumin-induced allergic rhinitis in mice, including sneeze/scratch, mast cell activation, eosinophil infiltration, and Syk activation. The treatment of ethanol extract signiï¬cantly suppressed the release of ß-hexosaminidase (a degranulation marker) and mRNA expression levels of various cytokines, including IL-3, IL-10, and IL-13 in activated RBL2H3 cells. The ethanol extract and ß-sitostenone, which was purified from the extract, could respectively reduce the Ca2+ ion mobilization in activated RBL-2H3 cells. Furthermore, results collected from western immunoblotting demonstrated that ethanol extract signiï¬cantly retarded Ca2+ ion mobilization-initiated signaling cascade, which provoked the expression of various allergic cytokines. Also, the extract incubation interfered with P38 as well as NF-kB activation and Nrf-2 translocation. Our study suggested that ethanol extract possessed some natural constituents which could inhibit immediate degranulation and de novo synthesis of allergic cytokines via inhibition of Ca2+ ion mobilization in mast cells in the nasal mucosa of allergic rhinitis mice.
Assuntos
Antialérgicos/farmacologia , Bombyx/metabolismo , Cordyceps/fisiologia , Carpóforos/fisiologia , Mucosa Nasal/efeitos dos fármacos , Rinite Alérgica/prevenção & controle , Animais , Antialérgicos/isolamento & purificação , Bombyx/embriologia , Sinalização do Cálcio , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Modelos Animais de Doenças , Etanol/química , Larva/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos Endogâmicos BALB C , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Ovalbumina , Ratos , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/imunologia , Rinite Alérgica/metabolismo , Solventes/químicaRESUMO
Zizyphus mauritiana Lam. seeds (ZMS) have been used medicinally as sedative or hypnotic drugs in most of Asian countries. ZMS has significant benefits to the human health. Therefore, we have evaluated immunomodulatory effect of lectin extracted from these ZMSL in both in vitro and in vivo study. Anaphylaxis is a severe life-threatening allergic reaction and Arthus reaction is deposition of immune complex and complement system activation, so we hypothesized that if ZMSL can protect these severe allergic diseases. We have studied the effect of ZMSL on macrophages and Wistar albino rats and confirmed its protective effect against anaphylaxis and Arthus reaction. Results of this study suggest ZMSL have immunostimulatory and antiallergic activity.
Assuntos
Adjuvantes Imunológicos/isolamento & purificação , Antialérgicos/isolamento & purificação , Fatores Imunológicos/isolamento & purificação , Lectinas/isolamento & purificação , Ziziphus/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Anafilaxia/prevenção & controle , Animais , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico , Reação de Arthus/prevenção & controle , Antígenos de Grupos Sanguíneos , Inativadores do Complemento/isolamento & purificação , Inativadores do Complemento/farmacologia , Inativadores do Complemento/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Hemaglutinação/efeitos dos fármacos , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Lectinas/farmacologia , Lectinas/uso terapêutico , Leucócitos/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Lisossomos/enzimologia , Macrófagos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Plantas Medicinais/química , Coelhos , Ratos Wistar , Sementes/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Asthma is a chronic inflammatory lung disorder with continuously increasing prevalence worldwide. Novel strategies are needed to prevent or improve asthma. The aim of this study was to investigate the effects of sophoricoside from Sophora japonica on allergic asthma. The mature seeds of S. japonica contain a large amount of sophoricoside. Sophoricoside reduced allergic and asthmatic symptoms by suppressing airway inflammation and antibody-antigen reaction in mouse models. In particular, sophoricoside suppressed immune cell recruitment into the airway lumens of the lungs and production of pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of ovalbumin (OVA)-induced mice. It also decreased the amounts of histamine and arachidonic acid metabolites released in OVA-induced mice and antibody-antigen stimulated mast cells. In addition, sophoricoside decreased differentiation of naïve CD4+ T cells into T helper type 1 (Th1), Th2, and Th17 cells. Overall, we demonstrated that sophoricoside improved allergic asthma by suppressing mast cell activation and CD4+ T cell differentiation.
Assuntos
Antialérgicos/farmacologia , Antiasmáticos/farmacologia , Benzopiranos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sophora , Animais , Antialérgicos/isolamento & purificação , Antiasmáticos/isolamento & purificação , Asma/tratamento farmacológico , Asma/imunologia , Asma/metabolismo , Benzopiranos/isolamento & purificação , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Degranulação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Liberação de Histamina/efeitos dos fármacos , Imunoglobulinas/metabolismo , Mediadores da Inflamação/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos Endogâmicos BALB C , Ovalbumina , Extratos Vegetais/isolamento & purificação , Sophora/químicaRESUMO
Asparagus (Asparagus officinalis L.) is one of the widely consumed vegetables. To investigate the mechanism underlying the anti-allergic responses of asparagus, we extracted different fractions from asparagus and measured their inhibitory effects on ß-hexosaminidase release in RBL-2H3 cells in vitro and an atopic dermatitis NC/Nga mouse model in vivo. The lipid fractions from asparagus were extracted with 50% ethanol, separated using chloroform by liquid-liquid phase separation, and fractionated by solid-phase extraction. Among them, acetone fraction (rich in glycolipid) and MeOH fraction (rich in phospholipid) markedly inhibited ß-hexosaminidase release from RBL-2H3 cells. In NC/Nga mice treated with picryl chloride, atopic dermatitis was alleviated following exposure to the 50% EtOH extract, acetone fraction, and methanol fraction. The inhibitory effects of asparagus fractions in vivo were supported by the significant decrease in serum immunoglobulin E (IgE) levels. The phospholipid fractions showed significantly better inhibitory effects, and phosphatidic acid from this fraction showed the best inhibitory effect on ß-hexosaminidase release. In mice challenged with ovalbumin (OVA), oral administration of asparagus extract and its fractions decreased the OVA-specific IgE level and total IgE, indicating that these effects may be partly mediated through the downregulation of antigen-specific IgE production. Taken together, the present study shows for the first time that asparagus extract and its lipid fractions could potentially mitigate allergic reactions by decreasing degranulation in granulocytes. Our study provides useful information to develop nutraceuticals and functional foods fortified with asparagus.
Assuntos
Antialérgicos/administração & dosagem , Asparagus/química , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/imunologia , Fosfolipídeos/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Feminino , Granulócitos/efeitos dos fármacos , Granulócitos/imunologia , Hexosaminidases/imunologia , Humanos , Imunoglobulina E/imunologia , Camundongos Endogâmicos BALB C , Fosfolipídeos/química , Fosfolipídeos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificaçãoRESUMO
Sargassum horneri (S. horneri), an edible brown alga, has been proposed as a functional food with an improvement effect on abnormal skin immune responses. The present study investigates the anti-allergic effect of an ethanol extract from S. horneri (SHE) on immunoglobulin E (IgE)/bovine serum albumin (BSA)-mediated activation in bone marrow-derived cultured-mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) reaction in mice. SHE markedly and dose-dependently suppressed the degranulation of BMCMCs by reducing the ß-hexosaminidase and histamine release without cytotoxicity. In addition, SHE significantly decreased the FcεRI expression on the surface of BMCMCs and its IgE binding. Moreover, SHE reduced the mRNA expression and the production of allergic cytokines; interleukin (IL)-1ß, IL-4, IL-5, IL-6, IL-10, IL-13; interferon (IFN)-γ and/or tumor necrosis factor (TNF)-α; and a chemokine, thymus and activation-regulated chemokine (TARC), by suppressing the activation of Src-family kinases and nuclear factor (NF)-κB signaling. In further study, the application of SHE reduced the PCA reaction in an IgE/BSA-induced type I allergic mice model. Taken together, we suggest that SHE has an anti-allergic effect in type I allergic responses.
Assuntos
Antialérgicos/farmacologia , Degranulação Celular/efeitos dos fármacos , Alimento Funcional , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade Imediata/prevenção & controle , Mastócitos/efeitos dos fármacos , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Receptores de IgE/metabolismo , Sargassum/metabolismo , Pele/efeitos dos fármacos , Ração Animal , Animais , Antialérgicos/isolamento & purificação , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Dinitrofenóis , Modelos Animais de Doenças , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Soroalbumina Bovina , Pele/imunologia , Pele/metabolismoRESUMO
As the expression level of allergic disease sensitive genes are correlated with the severity of allergic symptoms, suppression of these gene expressions could be promising therapeutics. We demonstrated that protein kinase Cδ / heat shock protein 90-mediated H1R gene expression signaling and nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression signaling are responsible for the pathogenesis of pollinosis. Treatment with Awa-tea combined with wild grape hot water extract suppressed these signaling and alleviated nasal symptoms in toluene-2,4-diisocyanate (TDI)-sensitized rats. However, the underlying mechanism of its anti-allergic activity is not elucidated yet. Here, we sought to identify an anti-allergic compound from Awa-tea and pyrogallol was identified as an active compound. Pyrogallol strongly suppressed ionomycin-induced up-regulation of IL-9 gene expression in RBL-2H3 cells. Treatment with pyrogallol in combination with epinastine alleviated nasal symptoms and suppressed up-regulation of IL-9 gene expression in TDI-sensitized rats. Pyrogallol itself did not inhibit calcineurin phosphatase activity. However, pyrogallol suppressed ionomycin-induced dephosphorylation and nuclear translocation of NFAT. These data suggest pyrogallol is an anti-allergic compound in Awa-tea and it suppressed NFAT-mediated IL-9 gene expression through the inhibition of dephosphorylation of NFAT. This might be the underlying mechanism of the therapeutic effects of combined therapy of pyrogallol with antihistamine. J. Med. Invest. 67 : 289-297, August, 2020.
Assuntos
Antialérgicos/farmacologia , Interleucina-9/genética , Pirogalol/farmacologia , Rinite Alérgica Sazonal/tratamento farmacológico , Chá/química , Animais , Antialérgicos/isolamento & purificação , Células Cultivadas , Fermentação , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Fatores de Transcrição NFATC/fisiologia , Pirogalol/isolamento & purificação , Pirogalol/uso terapêutico , Ratos , Ratos Endogâmicos BN , Tolueno 2,4-Di-Isocianato/farmacologiaRESUMO
Viridicatol is a quinoline alkaloid isolated from the deep-sea-derived fungus Penicillium griseofulvum. The structure of viridicatol was unambiguously established by X-ray diffraction analysis. In this study, a mouse model of ovalbumin-induced food allergy and the rat basophil leukemia (RBL)-2H3 cell model were established to explore the anti-allergic properties of viridicatol. On the basis of the mouse model, we found viridicatol to alleviate the allergy symptoms; decrease the levels of specific immunoglobulin E, mast cell protease-1, histamine, and tumor necrosis factor-α; and promote the production of interleukin-10 in the serum. The treatment of viridicatol also downregulated the population of B cells and mast cells (MCs), as well as upregulated the population of regulatory T cells in the spleen. Moreover, viridicatol alleviated intestinal villi injury and inhibited the degranulation of intestinal MCs to promote intestinal barrier repair in mice. Furthermore, the accumulation of Ca2+ in RBL-2H3 cells was significantly suppressed by viridicatol, which could block the activation of MCs. Taken together, these data indicated that deep-sea viridicatol may represent a novel therapeutic for allergic diseases.
Assuntos
Antialérgicos/farmacologia , Hidroxiquinolinas/farmacologia , Penicillium/química , Penicillium/metabolismo , Quinolonas/farmacologia , Anafilaxia/tratamento farmacológico , Animais , Antialérgicos/isolamento & purificação , Organismos Aquáticos/química , Organismos Aquáticos/metabolismo , Linfócitos B/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/etiologia , Histamina/sangue , Hidroxiquinolinas/química , Hidroxiquinolinas/isolamento & purificação , Imunoglobulina E/sangue , Interleucina-10/sangue , Intestinos/efeitos dos fármacos , Intestinos/patologia , Mastócitos/efeitos dos fármacos , Camundongos , Ovalbumina/toxicidade , Peptídeo Hidrolases/sangue , Quinolonas/química , Quinolonas/isolamento & purificação , Ratos , Linfócitos T Reguladores/metabolismo , Fator de Necrose Tumoral alfa/sangue , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
PURPOSE: It has been previously shown that the complete pharmacokinetic profile, in particular the elimination phase, of intranasal fluticasone furoate has not been fully characterized due to the inability to quantify concentrations at low enough levels. This study was designed to evaluate the pharmacokinetic profile of intranasal FF using a validated, ultra-sensitive analytical method in healthy subjects. METHODS: This was an open-label, single-dose, two-period, one-treatment, crossover study. A dose of 880 µg fluticasone furoate was administered intra nasally. Blood samples for pharmacokinetic analysis were collected at 23 time points up to 36 h and analyzed for FF plasma levels using a lower limit of quantitation (LLOQ) of 0.1 pg/mL. Medical and adverse events (AE) were monitored throughout the study. RESULTS: Eighteen subjects were enrolled in and 17 completed the study. The results showed that all 17 subjects had measurable fluticasone furoate plasma concentrations at all time points with a clearly defined elimination phase, thus allowing estimation of AUCinf and t1/2. Median Tmax was 1.33 h (range=0.75-6.00), mean Cmax was 13.05±7.59 pg/mL, mean AUCt was 148.48±77.76 pg/mL*h, mean AUCinf was 279.07±187.81 pg/mL*h, and mean t1/2 was 31.67±29.23 h. In total 4 subjects (22.2%) experienced 4 AEs. CONCLUSION: Using a lower LLOQ than what has been previously reported, a complete characterization of intranasal fluticasone furoate pharmacokinetics, including a clearly defined terminal elimination phase, was achieved. This method will allow for further investigations into the pharmacokinetics of fluticasone furoate.
Assuntos
Androstadienos/farmacocinética , Antialérgicos/farmacocinética , Administração Intranasal , Adulto , Androstadienos/administração & dosagem , Androstadienos/isolamento & purificação , Antialérgicos/administração & dosagem , Antialérgicos/isolamento & purificação , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Limite de Detecção , Masculino , Rinite Alérgica/tratamento farmacológico , Espectrometria de Massas em Tandem/métodosRESUMO
BACKGROUND: The study was aimed to investigate the protective effect of Asarum sieboldii Miq. essential oil (AEO) on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats. METHODS AND RESULTS: Sixty Sprague-Dawley male rats were randomly divided into six groups (n=10): control, model, cetirizine (Cet, 4.65 g/kg), and AEO (0.5, 1.5, 3 g/kg) groups. All animals except the control group received repeated intranasal instillation with 20 µl of 20% OVA in Al(OH)3 saline solvent for 15 days. The control group was intranasally instilled with 5 mg/ml of Al(OH)3 instead of the same procedure. In the 15 days, Cet and AEO were orally administrated for 28 days. At the end of the drug administration, 20 µl of 5% OVA was given to animals to stimulate allergic reaction, then the rat behavioral detection, assessment of the patho-morphological changes in nasal mucosa, and the serum biomarkers were determined. The result showed that AEO could significantly reduce the amount of nasal secretions, sneezing, and the degree of nasal scratching in AR rats with EC50 = 1.5 and 2.8 g/kg, respectively. The degree of nasal mucosal inflammation in AEO group improved, the levels of immunoglobulin E (IgE), histamine, IL-4, IL-5, IL-17 were decreased, and the level of IFN-γ was increased obviously with EC50 = 2 g/kg. CONCLUSION: The study suggested that the possible mechanism might be related with the inhibition of histamine release and regulation of the cytokine levels, which plays an important role in the treatment of AR.
Assuntos
Antialérgicos/farmacologia , Asarum , Medicamentos de Ervas Chinesas/farmacologia , Mucosa Nasal/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Rinite Alérgica/prevenção & controle , Animais , Antialérgicos/isolamento & purificação , Asarum/química , Comportamento Animal/efeitos dos fármacos , Citocinas/sangue , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Histamina/sangue , Imunoglobulina E/sangue , Masculino , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Óleos Voláteis/isolamento & purificação , Ovalbumina , Óleos de Plantas/isolamento & purificação , Ratos Sprague-Dawley , Rinite Alérgica/sangue , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/imunologiaRESUMO
CARAS is an airway inflammation of allergic individuals, with a type 2 immune response. The pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study evaluated the alkaloids warifteine (War) and methylwarifteine (Mwar) from Cissampelos sympodialis in CARAS experimental model. Therefore, BALB/c mice were ovalbumin (OVA) sensitized and challenged and treated with both alkaloids. Treated animals showed a decrease (p < 0.05) of allergic signs as sneezing and nasal rubbings, histamine nasal hyperreactivity, and inflammatory cell migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids, main eosinophils. In the systemic context, only Mwar reduced eosinophilia, however, both alkaloids reduced the serum levels of OVA-specific IgE. Histological analysis revealed that the alkaloids decreased the inflammatory cells into the subepithelial and perivascular regions of nasal tissue and the peribronchiolar and perivascular regions of lung tissue. Hyperplasia/hypertrophy of nasal and lung goblet cells were reduced in alkaloid treated animals; however, the treatment did not change the number of mast cells. The lung hyperactivity was attenuated by reducing hyperplasia of fibroblast and collagen fiber deposition and hypertrophy of the lung smooth muscle layer. The immunomodulatory effect was by decreasing of type 2 and 3 cytokines (IL-4/IL-13/IL-5 and IL-17A) dependent by the increasing of type 1 cytokine (IFN-γ) into the BALF of treated sick animals. Indeed, both alkaloids reduced the NF-кB (p65) activation on granulocytes and lymphocytes, indicating that the alkaloids shut down the intracellular transduction signals underlie the transcription of TH2 cytokine gens.
Assuntos
Alcaloides/farmacologia , Antialérgicos/farmacologia , Asma/tratamento farmacológico , Rinite Alérgica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/uso terapêutico , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Antialérgicos/uso terapêutico , Asma/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/imunologia , Cissampelos/química , Colágeno/metabolismo , Citocinas/sangue , Modelos Animais de Doenças , Eosinófilos/imunologia , Feminino , Imunoglobulina E/sangue , Inflamação/tratamento farmacológico , Pulmão/imunologia , Pulmão/patologia , Mastócitos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Muco/metabolismo , Líquido da Lavagem Nasal/imunologia , Mucosa Nasal/imunologia , Mucosa Nasal/patologia , Ovalbumina/imunologia , Ovalbumina/toxicidade , Rinite Alérgica/induzido quimicamente , Espirro/efeitos dos fármacosRESUMO
Marine seaweed polysaccharides have been considered as a potential resource for antiallergic therapy. Alginate is an acidic linear polysaccharide and soluble dietary fiber that was extracted from brown algae, Laminaria japonica. The molecular weight of alginate was 108 kDa, and its water solution exhibited non-Newtonian characteristics, including viscoelasticity and shear-thinning behavior. The ability of alginate to inhibit allergic reactions was investigated in ovalbumin (OVA)-induced BALB/c mice, which have been widely used as a mouse model of egg allergy. The results showed that alginate could effectively attenuate the occurrence of allergic reactions, including improving the integrity of the intestinal epithelial villi and inhibition of mast cell degranulation in the jejunum, in OVA-induced mice. Moreover, after treatment with alginate, the levels of IgE, histamine and IL-4 in OVA-induced mice were remarkably decreased, and the levels of IFN-γ were markedly increased. In addition, the number of Treg cells in spleen tissues in OVA-induced mice was increased by alginate, and the OVA-induced differentiation of Th0 cells into Th2 cells was significantly inhibited. These results demonstrate that alginate possesses potential antiallergic activities in a mouse model of egg allergy, which might provide important evidence that alginate, extracted from Laminaria japonica, can be developed into a novel functional food for inhibiting egg allergy.
Assuntos
Alginatos/farmacologia , Antialérgicos/farmacologia , Hipersensibilidade a Ovo , Alginatos/isolamento & purificação , Animais , Antialérgicos/isolamento & purificação , Modelos Animais de Doenças , Duodeno/citologia , Duodeno/efeitos dos fármacos , Hipersensibilidade a Ovo/metabolismo , Hipersensibilidade a Ovo/prevenção & controle , Feminino , Histamina/metabolismo , Imunoglobulina E/metabolismo , Laminaria/química , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Baço/citologia , Baço/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacosRESUMO
Chrysanthemum zawadskii var. latilobum (CZL) has been used in Eastern medicine for the treatment of various diseases, such as pneumonia, bronchitis, cough, the common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. In the present study, we isolated two strong antiallergic compounds from CZL, namely, eriodictyol-7-O-ß-d-glucuronide (EDG) and 5,7-dihydroxy-4-chromene (DC), and investigated their antiallergic effects in FcεRI-mediated human basophilic KU812F cells. EDG and DC downregulated the protein and messenger RNA (mRNA) expression of FcεRI on the cell surface. Moreover, Western blotting analysis showed that EDG and DC inhibited the expression of protein tyrosine kinases such as Syk and Lyn, and extracellular-regulated kinases (ERK) 1/2. These results suggested that EDG and DC, antiallergic constituents of CZL, are potential therapeutic candidates for protection against and for the treatment of allergic disorders.
Assuntos
Antialérgicos/isolamento & purificação , Basófilos/efeitos dos fármacos , Benzopiranos/farmacologia , Chrysanthemum/química , Flavanonas/farmacologia , Glucuronatos/farmacologia , Extratos Vegetais/farmacologia , Antialérgicos/farmacologia , Benzopiranos/química , Cálcio/metabolismo , Degranulação Celular/efeitos dos fármacos , Linhagem Celular , Flavanonas/isolamento & purificação , Glucuronatos/isolamento & purificação , Humanos , Sistema de Sinalização das MAP Quinases , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Proteínas Tirosina Quinases/metabolismo , Receptores de IgE/metabolismoRESUMO
Objectives: Sulforaphane, a major ingredient isolated from Brassica oleracea var. italica (broccoli), is known to exhibit anti-inflammatory, anti-cancer, and anti-diabetic effects. In this study, we employed an in vitro model of phorbol 12-myristate 13-acetate and a23187 (PMACI)-stimulated human mast cells (HMC-1 cells) to investigate the anti-allergic inflammatory effects and mechanisms of sulforaphane and Brassica oleracea var. italica extracts.Methods: Cytokine levels were measured by ELISA and quantitative real-time-PCR methods. Caspase-1 activity was determined by caspase-1 assay. Binding mode of sulforaphane within caspase-1 was determined by molecular docking simulation. Protein expression was determined by Western blotting.Results: Water extract of Brassica oleracea var. italica (WE) significantly reduced thymic stromal lymphopoietin (TSLP) secretion and caspase-1 activity on activated HMC-1 cells. In the molecular docking simulation and in vitro caspase-1 assays, sulforaphane regulated caspase-1 activity by docking with the identical binding site of caspase-1. Sulforaphane significantly inhibited the levels of inflammatory mediators including TSLP, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-8 in a dose-dependent manner. Immunoblotting experiments revealed that sulforaphane and WE reduced translocation of NF-κBp65 into the nucleus and phosphorylation of IκBα in the cytosol. Furthermore, phosphorylation of mitogen-activated protein kinases (MAPK) was down-regulated by treatment with sulforaphane or WE.Conclusion: Our findings suggest that sulforaphane and WE have anti-allergic inflammatory effects by intercepting caspase-1/NF-κB/MAPKs signaling pathways.