Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.385
Filtrar
1.
Scand J Immunol ; 91(3): e12856, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31794090

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease. A hallmark of AD is dry itchy skin that results from defects in the epidermal barrier function. Aloe vera is used widely to promote general health and is administered topically to treat skin conditions such as eczema, burns and wounds. However, effects of A vera on AD were not fully elucidated. In this study, we investigated the oral administration of processed A vera gel (PAG) containing low molecular weight Aloe polysaccharides to treat ovalbumin (OVA)-induced AD in mice. Oral administration of PAG suppressed total and OVA-specific IgE production in sera and decreased the epidermal thickness of skin. Numbers of Ki-67-positive cells were reduced by PAG treatment. Expression levels of tight junction genes, including those that encode ZO-1, Claudin-1 and Claudin-8, were decreased in AD skin lesions, whereas oral administration of PAG partially restored the expression levels of tight junction genes. In addition, IL-4 and IL-17A mRNA transcript levels were reduced in skin lesions after PAG treatment. Taken together, our findings suggest that oral administration of PAG ameliorated AD, normalized tight junction gene expression and suppressed inflammatory cytokines in AD skin.


Assuntos
Aloe/química , Antialérgicos/farmacologia , Dermatite Atópica/etiologia , Exsudatos de Plantas/farmacologia , Polissacarídeos/farmacologia , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/imunologia , Animais , Antialérgicos/química , Biomarcadores , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Mediadores da Inflamação/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/metabolismo , Camundongos , Ovalbumina/efeitos adversos , Exsudatos de Plantas/química , Polissacarídeos/química , Pele/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Pele/patologia
2.
BMC Complement Altern Med ; 19(1): 361, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829185

RESUMO

BACKGROUND: Moringa oleifera Lam. is a commonly used plant in herbal medicine and has various reported bioactivities such as antioxidant, antimicrobial, anticancer and antidiabetes. It is rich in nutrients and polyphenols. The plant also has been traditionally used for alleviating allergic conditions. This study was aimed to examine the anti-allergic activity of M. oleifera extracts and its isolated compounds. METHOD: M. oleifera leaves, seeds and pods were extracted with 80% of ethanol. Individual compounds were isolated using a column chromatographic technique and elucidated based on the nuclear magnetic resonance (NMR) and electrospray ionisation mass spectrometry (ESIMS) spectral data. The anti-allergic activity of the extracts, isolated compounds and ketotifen fumarate as a positive control was evaluated using rat basophilic leukaemia (RBL-2H3) cells for early and late phases of allergic reactions. The early phase was determined based on the inhibition of beta-hexosaminidase and histamine release; while the late phase was based on the inhibition of interleukin (IL-4) and tumour necrosis factor (TNF-α) release. RESULTS: Two new compounds; ethyl-(E)-undec-6-enoate (1) and 3,5,6-trihydroxy-2-(2,3,4,5,6-pentahydroxyphenyl)-4H-chromen-4-one (2) together with six known compounds; quercetin (3), kaempferol (4), ß-sitosterol-3-O-glucoside (5), oleic acid (6), glucomoringin (7), 2,3,4-trihydroxybenzaldehyde (8) and stigmasterol (9) were isolated from M. oleifera extracts. All extracts and the isolated compounds inhibited mast cell degranulation by inhibiting beta-hexosaminidase and histamine release, as well as the release of IL-4 and TNF-α at varying levels compared with ketotifen fumarate. CONCLUSION: The study suggested that M. oleifera and its isolated compounds potentially have an anti-allergic activity by inhibiting both early and late phases of allergic reactions.


Assuntos
Antialérgicos/farmacologia , Mastócitos/efeitos dos fármacos , Moringa oleifera , Extratos Vegetais/farmacologia , Animais , Antialérgicos/análise , Antialérgicos/química , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Frutas/química , Extratos Vegetais/análise , Extratos Vegetais/química , Folhas de Planta/química , Ratos
3.
Life Sci ; 238: 116953, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626793

RESUMO

AIMS: This study focused on investigating whether NS8593 reverses airway smooth muscle (ASM) contraction and the underlying mechanism. MAIN METHODS: ASM contraction in mouse tracheal rings and lung slices was measured. Currents mediated by voltage dependent Ca2+ channels (VDCCs) and ACH-activated channels were measured using the whole-cell patch-clamp technique in single tracheal smooth muscle cells (TSMCs). Intracellular Ca2+ level and cell length were measured using an LSM 700 laser confocal microscope and a Zen 2010 software. Mouse respiratory system resistance (Rrs) was assessed using a FlexiVent FX system. KEY FINDINGS: High K+ (80 mM K+) and ACH induced ASM contraction in mouse tracheal rings and lung slices, which was partially relaxed by nifedipine (blocker of L-type VDCCs, LVDCCs), YM-58483 (blocker of store-operated Ca2+ entry (SOCE), transient receptor potential C3 (TRPC3) and TRPC5 channels), respectively. However, the contraction was completely reversed by NS8593, whereas, slightly relaxed by formoterol. ACH activated inward currents, which displayed linear and reversed around 0 mV, indicating the currents were mediated by non-selective cation channels (NSCCs). Moreover, these currents were blocked by YM-58483. In addition, such currents were abolished by NS8593, implicating that NS8593 inhibits the same channels. Besides, NS8593 inhibited increases of intracellular Ca2+ and the associated cell shortening. Finally, NS8593 inhibited ACH-induced increases of mouse respirator system resistance (Rrs). SIGNIFICANCE: Our results indicate that NS8593 inhibits LVDCCs and NSCCs, resulting in decreases of intracellular Ca2+ and then leading to ASM relaxation. These data suggest that NS8593 might be a new bronchodilator.


Assuntos
1-Naftilamina/análogos & derivados , Asma/tratamento farmacológico , Canais de Cálcio Tipo L/química , Cálcio/metabolismo , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , 1-Naftilamina/farmacologia , Animais , Antialérgicos/farmacologia , Asma/induzido quimicamente , Asma/patologia , Canais de Cálcio Tipo L/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Músculo Liso/metabolismo , Músculo Liso/patologia , Ovalbumina/toxicidade
4.
Chin J Nat Med ; 17(7): 525-534, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514984

RESUMO

This study aimed to investigate the mechanisms of Yu-Ping-Feng-San (YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis (AD). AD mouse model was established with fluorescein isothiocyanate (FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells (DCs) and group 2 innate lymphoid cells (ILC2s) were detected by flow cytometry. Human immortalized keratinocyte (HaCaT) cells were stimulated with Poly(I:C)/TNF-α in vitro to assessthymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and nuclear factor-κB (NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay (ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.


Assuntos
Antialérgicos/uso terapêutico , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/prevenção & controle , Animais , Antialérgicos/farmacologia , Linhagem Celular , Células Dendríticas/patologia , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células Epiteliais/metabolismo , Fluoresceína-5-Isotiocianato/toxicidade , Inflamação/metabolismo , Inflamação/patologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Linfócitos/metabolismo , Linfócitos/patologia , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
5.
Int Immunopharmacol ; 75: 105830, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31437788

RESUMO

Umbelliferone (UMB) is a coumarin derivative present in roots and barks of plants, such as Angelica decursiva, Artemisia capillaris, and orange. UMB has been previously reported to exhibit anti-inflammatory, anti-diabetic, and anti-cancer effects. However, the effect of UMB on atopic dermatitis (AD) remains unknown. The purpose of this study was to investigate the anti-atopic effects of UMB on 2,4-dinitrochlorobenzene (DNCB)- and house dust mite extract (Dermatophagoides farinae extract, DFE)-treated mice with AD-like skin lesions and on tumor necrosis factor (TNF)-α/interferon (IFN)-γ-treated HaCaT cells. In DNCB/DFE-treated mice, oral administration of UMB (20 and 40 mg/kg) for 28 days led to a significant decrease in ear thickness, spleen size and weight, serum levels of immunoglobulin E (IgE), IgG1, IgG2a, TNF-α, and interleukin 4 (IL-4), and mast cell infiltration; it also led to the suppression of pro-inflammatory cytokines and chemokines. In addition, UMB reduced the secretion of pro-inflammatory cytokines and chemokines in TNF-α/IFN-γ-treated HaCaT cells via regulation of MAPK, IkB-α/NF-κB, and STAT1 signaling pathways. Taken together, these results indicate that UMB ameliorates AD-associated symptoms and inflammation via regulation of various signaling pathways, suggesting that UMB might be a potential therapeutic agent of AD.


Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Umbeliferonas/uso terapêutico , Animais , Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Antígenos de Dermatophagoides , Linhagem Celular , Citocinas/sangue , Citocinas/genética , Citocinas/imunologia , Dermatite Atópica/sangue , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Dinitroclorobenzeno , Humanos , Queratinócitos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Pele/efeitos dos fármacos , Pele/patologia , Umbeliferonas/farmacologia
6.
Pharm Nanotechnol ; 7(4): 314-327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31362666

RESUMO

BACKGROUND: Development of polymeric micelles for the management of allergic conjunctivitis to overcome the limitations of topical installation, such as poor patient compliance, poor stromal permeability, and significant adverse effects, increase precorneal residence time and efficacy, and also control the release of drug at the target site. OBJECTIVE: The investigation was aimed at developing a polymeric micellar system of Azelastine HCl for Ocular Delivery. METHODS: Drug loaded micelles of tri-block copolymers Pf 127 were prepared by Thin Film hydration method. The polymeric micelles formulations (F1 to F9) were assessed for entrapment efficiency, micelle size, in vitro permeation, ex vivo transcorneal permeation, in vivo Ocular Irritation, and Histology. RESULTS: Optimized micelles formulation (F3), with the lowest micelle size of 92 nm, least polydispersity value of 0.135, highest entrapment efficiency of 95.30 ± 0.17%, and a cumulative drug permeation of 84.12 ± 1.26% in 8h, was selected to develop pH-sensitive micelles loaded carbopol in situ gel. The optimized in situ gel (G4) proved to be superior in its ex vivo transcorneal permeation when compared with Market Preparation and pure drug suspension, exhibiting 43.35 ± 1.48% Permeation with zero-order kinetics (r2 = 0.9944) across goat cornea. Transmission Electron microscopy revealed spherical polymeric micelles trapped in the gel matrix. A series of experiments showed hydration capability, non-irritancy, and histologically safe gel formulation that had appropriate handling characteristics. CONCLUSION: A controlled release pH-sensitive ocular formulation capable of carrying the drug to the anterior section of the eye via topical delivery was successfully developed for the treatment of allergic conjunctivitis.


Assuntos
Antialérgicos , Portadores de Fármacos/química , Ftalazinas , Administração Oftálmica , Animais , Antialérgicos/química , Antialérgicos/farmacologia , Preparações de Ação Retardada , Micelas , Ftalazinas/química , Ftalazinas/farmacologia , Poloxâmero/química
7.
Molecules ; 24(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426284

RESUMO

Allergic disease is one of the most important and common health problems worldwide. We have previously demonstrated that a fig leaf-derived lactic acid bacterium Lactobacillus (Lb.) paracasei IJH-SONE68 produces a novel exopolysaccharide (EPS). Furthermore, we have shown that the EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.36) promoting inflammatory reactions. To evaluate the anti-allergy and anti-inflammatory effects of the EPS, in the present study, we employed the picryl-chloride-induced delayed-type (type IV) allergy model mice, which is used to evaluate the contact dermatitis. Oral administration of the EPS was observed to reduce the ear swelling in the model mice. We also observed that the overexpression of ear interleukin-4 (T helper (Th) 2 cytokine) mRNA and the increase in serum immunoglobulin E (IgE) are repressed. However, the expression of interferon-γ (Th1 cytokine) was not accelerated in all of the allergen-challenged model mice. The improvement may be responsible for the Th2 downregulation rather than the Th1 upregulation. In addition, the symptom of immediate-type (type I) allergy model mice was improved by oral administration of the IJH-SONE68 cell (data not shown). We can conclude that the IJH-SONE68-derived EPS is useful to improve the type I and IV allergies including atopic dermatitis.


Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Dermatite de Contato/prevenção & controle , Fármacos Dermatológicos/farmacologia , Lactobacillus paracasei/química , Polissacarídeos Bacterianos/farmacologia , Administração Oral , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Antialérgicos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Dermatite de Contato/etiologia , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Fármacos Dermatológicos/isolamento & purificação , Modelos Animais de Doenças , Orelha , Expressão Gênica/efeitos dos fármacos , Hialuronoglucosaminidase/antagonistas & inibidores , Hialuronoglucosaminidase/imunologia , Hialuronoglucosaminidase/metabolismo , Imunoglobulina E/sangue , Imunoglobulina E/genética , Interferon gama/genética , Interferon gama/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Lactobacillus paracasei/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Cloreto de Picrila/administração & dosagem , Polissacarídeos Bacterianos/isolamento & purificação , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
8.
Int Arch Allergy Immunol ; 180(1): 10-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31234191

RESUMO

BACKGROUND: Shrimp-derived allergen has a serious impact on people's health. Chitosan oligosaccharide (COS) has anti-allergic action but its function on shrimp allergen-induced allergy and related molecular mechanisms remain unclear. METHODS: COS and its degrees of polymerization (DP) were selected to interact with shrimp tropomyosin (TM) and IgE was measured. A mouse model of food allergy was established by receiving shrimp TM intraperitoneally. The models were treated with different concentrations of COS. Fecal and serum histamine, serum IgE, IgG1 and IgG2a, and inflammatory cytokines were measured. RESULTS: The main products for COS were DP2-6 with the contents of 6, 40, 26, 16, and 4%, respectively, and reacted with shrimp TM increasingly when COS DP was increased. Severe symptoms of food allergy were observed in the TM group (diarrhea, anaphylactic response, and rectal temperature). In contrast, COS treatment improved these symptoms significantly (p < 0.05). The sensitized mice were desensitized after they were treated with 1 mg/kg COS. COS treatment significantly reduced serum IgE and IgG1 levels, and increased IgG2a levels (p < 0.05). COS consumption decreased fecal and serum histamine. COS treatment reduced Th2 cytokine (IL-4, IL-5, and IL-13) levels and increased the Th1 cytokine (IFN-γ) level (p < 0.05). CONCLUSIONS: COS showed anti-allergy properties by regulating the levels of Th1 and Th2 cytokines.


Assuntos
Alérgenos/imunologia , Antialérgicos/farmacologia , Quitosana , Crustáceos , Hipersensibilidade Alimentar/imunologia , Oligossacarídeos/farmacologia , Células Th1/imunologia , Células Th2/imunologia , Tropomiosina/imunologia , Animais , Antialérgicos/química , Quitosana/química , Citocinas/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/metabolismo , Liberação de Histamina/efeitos dos fármacos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Oligossacarídeos/química , Fenótipo , Células Th1/metabolismo , Células Th2/metabolismo
9.
Nutrients ; 11(6)2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31181780

RESUMO

Allium genus plants, such as leek (Allium porrum), are rich sources of anti-inflammatory and anti-oxidant secondary metabolites; this is of interest because it demonstrates their suitability as pharmacological alternatives for inflammatory processes, including allergy treatment. The composition of methanolic leek extract (LE) was analyzed by GC-MS and LC-IT/MS, and the total phenolic content and antioxidant capacity were quantified by colorimetric methods. Its pharmacological potential was analyzed in human bronchial epithelial Calu-3 cells, human mast cells LAD2, and humanized rat basophiles RBL-2H3. LE exhibited a cytotoxic effect on Calu-3 cells and HumRBL-2H3 cells only at high concentrations and in a dose-dependent manner. Moreover, LE decreased the degranulation of LAD2 and HumRBL-2H3 cells. LE treatment also significantly prevented alterations in transepithelial electrical resistance values and mRNA levels of glutathione-S-transferase (GST), c-Jun, and NFκB after treatment with H2O2 in ALI-cultured Calu-3 cells. Finally, ALI-cultured Calu-3 cells treated with LE showed lower permeability to Ole e 1 compared to untreated cells. A reduction in IL-6 secretion in ALI-cultured Calu-3 cells treated with LE was also observed. In summary, the results obtained in this work suggest that A. porrum extract may have potential anti-allergic effects due to its antioxidant and anti-inflammatory properties. This study provides several important insights into how LE can protect against allergy.


Assuntos
Antialérgicos/farmacologia , Brônquios/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Cebolas/química , Fenóis/uso terapêutico , Animais , Antialérgicos/análise , Antialérgicos/uso terapêutico , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/análise , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Brônquios/citologia , Brônquios/metabolismo , Linhagem Celular , Humanos , Hipersensibilidade/metabolismo , Hipersensibilidade/prevenção & controle , Inflamação/metabolismo , Inflamação/prevenção & controle , Mediadores da Inflamação/metabolismo , Fenóis/análise , Fenóis/farmacologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos
10.
Int J Mol Sci ; 20(10)2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137528

RESUMO

Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.


Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Alcamidas Poli-Insaturadas/uso terapêutico , Animais , Antialérgicos/administração & dosagem , Antialérgicos/farmacologia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Dinitroclorobenzeno/toxicidade , Feminino , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Alcamidas Poli-Insaturadas/administração & dosagem , Alcamidas Poli-Insaturadas/farmacologia
11.
Arch Pharm Res ; 42(9): 754-765, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31049823

RESUMO

Allergic patients have life-long chronic inflammatory diseases with repeated relapses and exacerbations. Currently used allergy therapeutics have some limitations, which warrants a search for novel drug targets for allergy treatment. The studies on conventional allergic disease therapeutics have been focused on the pathology of allergy involving effector type 2 helper T cells (Th2). However, it has been suggested that allergen-specific memory Th2 cells are developed after the initial allergen exposure, which may play a critical role in the allergic relapses. Here, we discuss the contribution of memory Th2 cells to allergic diseases and the microenvironmental factors for chronic allergic disease persistence. Since most allergy drugs are prescribed to suppress symptoms of the diseases, targeting the different types of cells or factors contributing to allergic diseases persistence may cure the disease.


Assuntos
Antialérgicos/farmacologia , Homeostase/efeitos dos fármacos , Hipersensibilidade/tratamento farmacológico , Memória Imunológica/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Animais , Antialérgicos/química , Humanos , Hipersensibilidade/imunologia , Memória Imunológica/imunologia
12.
J Sep Sci ; 42(14): 2351-2359, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31050150

RESUMO

Saposhnikoviae Radix, the dried root of Saposhnikoviae divaricata, is commonly used in the traditional Chinese anti-allergic preparations, like Bofutsusho-san and Yupingfeng granules. A high-expression Mas-related G protein-coupled receptor X2 cell membrane chromatography coupled online with high-performance liquid chromatography combined with an ion trap time-of-flight multistage mass spectrometry system was established and used for screening and identifying the anti-allergic components in Saposhnikoviae Radix. The system was validated for excellent specificity and suitability using the appropriate standards. Two retained fractions were obtained on the cell membrane chromatography column, and three main components were identified as prim-O-glucosylcimifugin, cimifugin, and 4'-O-ß-d-glucosyl-5-O-methylvisamminol. Next, the molecular docking study was conducted, which confirmed that these three components could effectively bind to MRGPRX2 through hydrogen bonds with its amino acid residues. Finally, histamine release assay was performed to investigate the bioactivities of prim-O-glucosylcimifugin, cimifugin, and 4'-O-ß-d-glucosyl-5-O-methylvisamminol. Results showed that these three components could exert anti-allergic effects by inhibiting the histamine release in a dose-dependent manner (from 10 to 100 µM). In conclusion, the high-expression Mas-related G protein-coupled receptor X2 cell membrane chromatography is an effective tool for discovering the anti-allergic components in Saposhnikoviae Radix.


Assuntos
Antialérgicos/análise , Apiaceae/química , Membrana Celular/química , Avaliação Pré-Clínica de Medicamentos , Proteínas do Tecido Nervoso/química , Receptores Acoplados a Proteínas-G/química , Receptores de Neuropeptídeos/química , Antialérgicos/farmacologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Composição de Medicamentos , Histamina/metabolismo , Humanos , Espectrometria de Massas , Simulação de Acoplamento Molecular
13.
Biochim Biophys Acta Mol Basis Dis ; 1865(6): 1690-1700, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30978390

RESUMO

Mast cell (MC) deficiency in KitW-sh/W-sh mice and inhibition with disodium chromoglycate (DSCG) or ketotifen reduced obesity and diabetes in mice on a high-cholesterol (1.25%) Western diet. Yet, Kit-independent MC-deficient mice and mice treated with DSCG disproved MC function in obesity and diabetes when mice are fed a high-fat diet (HFD) that contains no cholesterol. This study reproduced the obesity and diabetes inhibitory activities of DSCG and ketotifen from mice on a Western diet. Yet, such inhibitory effects were diminished in mice on the HFD. DSCG and ketotifen MC inhibitory activities were recovered from mice on the HFD supplemented with the same amount of cholesterol (1.25%) as that in the Western diet. DSCG and ketotifen effectively blunted the high-cholesterol diet-induced elevations of blood histamine and adipose tissue MC degranulation. Pearson's correlation test demonstrated significant and positive correlations between plasma histamine and total cholesterol or low-density lipoprotein-cholesterol (LDL). In cultured bone marrow-derived MCs, plasma from mice following a Western diet or a cholesterol-supplemented HFD, but not those from HFD-fed mice, induced MC degranulation and the release of ß-hexosaminidase, histamine, and serotonin. IgE, LDL, very low-density lipoprotein, and high-density lipoprotein also induced MC activation, which can be inhibited by DSCG and ketotifen depending on the doses and types of MC inhibitors and cholesterol, and also the MC granule molecules of interest. DSCG or ketotifen lost their activities in inhibiting LDL-induced activation of MCs from LDL receptor-deficient mice. These results indicate that dietary cholesterol critically influences the function of mouse MCs.


Assuntos
Degranulação Celular/efeitos dos fármacos , Colesterol na Dieta/efeitos adversos , Diabetes Mellitus Experimental/sangue , Mastócitos/efeitos dos fármacos , Obesidade/sangue , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Antialérgicos/farmacologia , Antiasmáticos/farmacologia , LDL-Colesterol/metabolismo , Cromolina Sódica/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica/efeitos adversos , Expressão Gênica , Histamina/sangue , Cetotifeno/farmacologia , Masculino , Mastócitos/metabolismo , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/etiologia , Obesidade/patologia , Receptores de LDL/deficiência , Receptores de LDL/genética , Serotonina/metabolismo , Transdução de Sinais , Estreptozocina , beta-N-Acetil-Hexosaminidases/metabolismo
14.
Inflamm Res ; 68(5): 387-395, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30874868

RESUMO

OBJECTIVE: AST2017-01 is developed to be used for treatment and prevention of allergic diseases and composed of processed-Cordyceps militaris and processed-Rumex crispus. But, effect of AST2017-01 remains unclear in an allergic rhinitis (AR). So, this study aimed to explore the effects of AST2017-01 in ovalbumin (OVA)-induced AR animal model. METHODS: OVA-induced AR animals were orally administered AST2017-01 and chrysophanol, an active component of AST2017-01 for 10 days. RESULTS: In mice with AR, AST2017-01 and chrysophanol markedly decreased number of rubs, IgE, histamine, thymic stromal lymphopoietin, tumor necrosis factor-α, interleukin (IL)-1ß, IL-4, IL-5, and IL-13 in serum or nasal mucosa tissues. Moreover, activities and protein levels of caspase-1 were markedly diminished by oral administration of AST2017-01 and chrysophanol. Declines of macrophage inflammatory protein-2, intercellular adhesion molecules-1, eosinophil, and mast cells were also noted in nasal mucosa tissues of AST2017-01 and chrysophanol groups. CONCLUSIONS: Taken together, these findings indicate that AST2017-01 has an anti-allergic effect as a therapeutic agent or functional food for treating and preventing AR.


Assuntos
Antialérgicos/uso terapêutico , Cordyceps , Rinite Alérgica/tratamento farmacológico , Rumex , Animais , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Antialérgicos/farmacologia , Caspase 1/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Feminino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Camundongos Endogâmicos BALB C , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ovalbumina , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Rinite Alérgica/imunologia
15.
J Nat Med ; 73(3): 608-613, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30847756

RESUMO

As a part of the investigation of the safety and efficacy of the cultivated Coptis japonica rhizome extracts using an artificial hydroponic cultivation system, the mutagenetic and anti-allergic activities were evaluated. Some extracts of commercial crude drugs of Coptis sp. were also evaluated for the comparison. None of the extracts showed a significant mutagenicity in Salmonella typhimurium TA102 by the Ames tests, but all the extracts showed in S. typhimurium TA98. The extracts of the hydroponically cultivated rhizomes showed anti-allergic activities against contact hypersensitivity as well as those of commercial crude drugs of Coptis sp. These results suggested the potential of the hydroponically cultivated rhizomes as one of the alternative sources for the medicinal usage.


Assuntos
Antialérgicos/farmacologia , Berberina/análise , Coptis/química , Coptis/imunologia , Mutagênicos/química , Extratos Vegetais/farmacologia , Antialérgicos/química , Berberina/química , Dermatite de Contato , Hidroponia , Extratos Vegetais/química , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
16.
Appl Microbiol Biotechnol ; 103(8): 3249-3264, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30852659

RESUMO

Diepoxy-containing compounds are widely distributed in nature. These metabolites are found in plants and marine organisms and are also produced by many microorganisms, fungi, or fungal endophytes. Many of these metabolites are antibiotics and exhibit a wide variety of biological activities. More than 80 α,ß-diepoxy-containing compounds are presented in this article, which belong to different classes of chemical compounds including lipids, terpenoids, alkaloids, quinones, hydroquinones, and pyrones. The main activities that characterize α,ß-diepoxy-containing compounds are antineoplastic with confidence up to 99%, antifungal with confidence up to 94%, antiinflammatory with confidence up to 92%, or antibacterial with confidence up to 78%. In addition, these metabolites can be used as a lipid metabolism regulator with a certainty of up to 81%, antiviral (Arbovirus) activity with a certainty of up to 71%, or antiallergic activity with confidence up to 69%. These data on the biological activity of diepoxy-containing compounds are of considerable interest to pharmacologists, chemists, and medical professionals who are involved in phytomedicine and related areas of science and industry.


Assuntos
Produtos Biológicos/farmacologia , Compostos de Epóxi/farmacologia , Animais , Antialérgicos/química , Antialérgicos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Produtos Biológicos/química , Compostos de Epóxi/química , Fungos/química , Insetos/química , Plantas/química , Plantas/microbiologia
17.
J Drugs Dermatol ; 18(2): 213-214, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30811151

RESUMO

Darier disease is an autosomal dominant genodermatosis of abnormal keratinization characterized by hyperkeratotic papules and plaques with a predilection for seborrheic areas. We report a case of a rare vesiculobullous variant of treatment-resistant Darier disease in a 55-year-old woman that failed topical tacrolimus and topical and oral glucocorticoids. Cetirizine was initiated at 10 mg daily and increased to 40 mg daily over four weeks, with resultant marked improvement of the patient's burning sensation. A punch biopsy revealed a perivascular infiltrate of eosinophils. This patient's symptomatic improvement with cetirizine, which has antagonizing properties against eosinophils, highlights the potential role of eosinophils in the pathogenesis of vesiculobullous Darier disease. We suggest that major basic protein secreted by eosinophils may propagate blister formation in vesiculobullous Darier disease by disrupting desmosomes. J Drugs Dermatol. 2019;18(2):213-214.


Assuntos
Antialérgicos/uso terapêutico , Cetirizina/uso terapêutico , Doença de Darier/tratamento farmacológico , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Antialérgicos/farmacologia , Cetirizina/farmacologia , Doença de Darier/complicações , Doença de Darier/diagnóstico , Relação Dose-Resposta a Droga , Eosinófilos/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Dermatopatias Vesiculobolhosas/complicações , Dermatopatias Vesiculobolhosas/diagnóstico , Resultado do Tratamento
18.
J Ethnopharmacol ; 236: 484-494, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30738115

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tibetan medicine has been practiced for 3800 years. Anzhijinhua San (AZJHS), which is a traditional Tibetan medicine, has been effective in the treatment of indigestion, anorexia and cold diarrhea. However, the effects of AZJHS on allergic diarrhea have not been reported. AIM OF THE STUDY: The aim of the present study was to elucidate the effect of AZJHS on experimental ovalbumin-induced diarrhea and elucidate its possible mechanism. MATERIALS AND METHODS: Female BALB/c mice were sensitized by intraperitoneal injection with 50 µg ovalbumin (OVA) and 1 mg alum in saline twice during a 2-week period. From day 28, mice were orally challenged with OVA (50 mg) every other day for a total of ten times. AZJHS (46.8 and 468.0 mg/kg) was orally administered every other day from day 0-46. Food allergy symptoms were evaluated. OVA- specific IgE, 5-HT and its metabolites in serum were determined. Immunohistochemical and histopathology were performed in gastrointestinal tract tissues. 5-HT-related gene expression was assayed in the colon. RESULTS: Severe symptoms of allergic diarrhea were observed in the model group (diarrhea, anaphylactic response, and rectal temperature). AZJHS (46.8 and 468.0 mg/kg) significantly reduced mouse diarrhea and significantly prevented the increases in OVA-specific IgE levels (P < 0.05), which challenge with OVA. AZJHS (46.8 and 468.0 mg/kg) significantly prevented the increases in 5-HT-positive cells. The nuclei of EC cells in the AZJHS (46.8 and 468.0 mg/kg) group increased in size and the secretory granules were fewer in number compared with those in the model group. AZJHS (46.8 and 468.0 mg/kg) significantly increased the relative fold changes of 5-HTP and 5-HT compared with the model group. The mRNA expression of the serotonin transporter (Sert) and serotonin receptor 3A (Htr3a) was significantly decreased after the 10th challenge with OVA, and AZJHS (46.8 and 468.0 mg/kg) significantly increased these levels. CONCLUSIONS: We demonstrated that the administration of AZJHS attenuated OVA-induced diarrhea by regulating the serotonin pathway. These results indicated that AZJHS may be a potential candidate as an anti-allergic diarrhea agent.


Assuntos
Antialérgicos/farmacologia , Diarreia/tratamento farmacológico , Hipersensibilidade Alimentar/tratamento farmacológico , Medicina Tradicional Tibetana/métodos , Extratos Vegetais/farmacologia , Animais , Antialérgicos/uso terapêutico , Diarreia/imunologia , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/imunologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Extratos Vegetais/uso terapêutico , Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
19.
Molecules ; 24(4)2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30791382

RESUMO

The proteolytic digest of milk casein, known as casein phosphopeptide (CPP-III), exhibits diverse biological activities, including calcium absorption and antioxidant activities. We hypothesized that the additional phosphorylation of this peptide can enhance its immunomodulatory activity such as suppression of allergy-associated cytokine and antigen-specific immune response. This study was conducted to assess whether oral intake of additionally phosphorylated CPP-III (P-CPP) attenuates ovalbumin (OVA)-induced IgE-mediated allergic reactions because of the additional phosphate groups. Female BALB/c mice were intraperitoneally sensitized with OVA twice at intervals of 14 days and then orally fed native CPP-III (N-CPP), P-CPP, and dephosphorylated CPP-III (D-CPP) for 6 weeks. Next, the mice were orally challenged with 50 mg of OVA. Oral administration of P-CPP suppressed total and specific IgE levels in the serum. Mice fed P-CPP exhibited low levels of OVA-specific IgG1 and increased OVA-specific IgG2a. P-CPP also suppressed IL-4 production, while D-CPP showed similar a level compared to that of the control. Further, P-CPP increased the population of the T follicular helper (Tfh) cell in the spleen. These results suggest that additional phosphorylation of CPP can enhance the attenuation of allergen-specific IgE-modulated allergic reactions in a murine food allergy model.


Assuntos
Antialérgicos/farmacologia , Caseínas/química , Leite/química , Ovalbumina/imunologia , Fosfopeptídeos/farmacologia , Animais , Antialérgicos/administração & dosagem , Antialérgicos/química , Temperatura Corporal , Imunomodulação/efeitos dos fármacos , Camundongos , Fosfopeptídeos/administração & dosagem , Fosfopeptídeos/química , Fosforilação , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
20.
Front Immunol ; 10: 175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30792720

RESUMO

Allergies and asthma are a major cause of chronic disease whose prevalence has been on the rise. Allergic disease including seasonal rhinitis, atopic dermatitis, urticaria, anaphylaxis, and asthma, are associated with activation of tissue-resident mast cells and circulating basophils. Although these cells can be activated in different ways, allergic reactions are normally associated with the crosslinking of the high affinity Fc receptor for Immunoglobulin E, FcεRI, with multivalent antigen. Inflammatory mediators released from cytoplasmic granules, or biosynthesized de novo, following FcεRI crosslinking induce immediate hypersensitivity reactions, including life-threatening anaphylaxis, and contribute to prolonged inflammation leading to chronic diseases like asthma. Thus, inappropriate or unregulated activation of mast cells and basophils through antigenic crosslinking of FcεRI can have deleterious, sometimes deadly, consequences. Accordingly, FcεRI has emerged as a viable target for the development of biologics that act to inhibit or attenuate the activation of mast cells and basophils. At the forefront of these strategies are (1) Anti-IgE monoclonal antibody, namely omalizumab, which has the secondary effect of reducing FcεRI surface expression, (2) Designed Ankyrin Repeat Proteins (DARPins), which take advantage of the most common structural motifs in nature involved in protein-protein interactions, to inhibit FcεRI-IgE interactions, and (3) Fusion proteins to co-aggregate FcεRI with the inhibitory FcγRIIb. This review presents the published research studies that support omalizumab, DARPins, and fusion proteins as, arguably, the three most currently viable strategies for inhibiting the expression and activation of the high affinity FcεRI on mast cells and basophils.


Assuntos
Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Imunoglobulina E/imunologia , Receptores de IgE/metabolismo , Transdução de Sinais , Animais , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico , Basófilos/efeitos dos fármacos , Basófilos/imunologia , Basófilos/metabolismo , Humanos , Hipersensibilidade/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Omalizumab/farmacologia , Omalizumab/uso terapêutico , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA