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4.
Molecules ; 26(3)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525733

RESUMO

Phyllanthus amarus Schum. & Thonn. (Phyllanthaceae) is a medicinal plant that is commonly used to treat diseases such as asthma, diabetes, and anemia. This study aimed to examine the antiallergic activity of P. amarus extract and its compounds. The antiallergic activity was determined by measuring the concentration of allergy markers release from rat basophilic leukemia (RBL-2H3) cells with ketotifen fumarate as the positive control. As a result, P. amarus did not stabilize mast cell degranulation but exhibited antihistamine activity. The antihistamine activity was evaluated by conducting a competition radioligand binding assay on the histamine 1 receptor (H1R). Four compounds were identified from the high performance liquid chromatography (HPLC) analysis which were phyllanthin (1), hypophyllanthin (2), niranthin (3), and corilagin (4). To gain insights into the binding interactions of the most active compound hypophyllanthin (2), molecular docking was conducted and found that hypophyllanthin (2) exhibited favorable binding in the H1R binding site. In conclusion, P. amarus and hypophyllanthin (2) could potentially exhibit antiallergic activity by preventing the activation of the H1 receptor.


Assuntos
Antialérgicos/farmacologia , Hipersensibilidade/tratamento farmacológico , Phyllanthus/química , Extratos Vegetais/farmacologia , Animais , Antialérgicos/química , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/métodos , Glucosídeos/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Taninos Hidrolisáveis/farmacologia , Hipersensibilidade/metabolismo , Cetotifeno/farmacologia , Lignanas/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Extratos Vegetais/química , Ratos , Receptores Histamínicos/metabolismo
5.
Int J Biol Macromol ; 171: 389-397, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33428960

RESUMO

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 Matriz
6.
Phytomedicine ; 80: 153391, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33113502

RESUMO

BACKGROUND: Pseudo-allergic reactions are potentially fatal hypersensitivity responses caused by mast cell activation. α-linolenic acid (ALA) is known for its anti-allergic properties. However, its potential anti-pseudo-allergic effects were not much investigated. PURPOSE: To investigate the inhibitory effects of ALA on IgE-independent allergy in vitro, and in vivo, as well as the mechanism underlying its effects. METHODS/STUDY DESIGNS: The anti-anaphylactoid activity of ALA was evaluated in passive cutaneous anaphylaxis reaction (PCA) and systemic anaphylaxis models. Calcium imaging was used to assess intracellular Ca2+ mobilization. The release of cytokines and chemokines was measured using enzyme immunoassay kits. Western blot analysis was conducted to investigate the molecules of Lyn-PLCγ-IP3R-Ca2+ and Lyn-p38/NF-κB signaling pathway. RESULTS: ALA (0, 1.0, 2.0, and 4.0 mg/kg) dose-dependently reduced serum histamine, chemokine release, vasodilation, eosinophil infiltration, and the percentage of degranulated mast cells in C57BL/6 mice. In addition, ALA (0, 50, 100, and 200 µM) reduced Compound 48/80 (C48/80) (30 µg/ml)-or Substance P (SP) (4 µg/ml)-induced calcium influx, mast cell degranulation and cytokines and chemokine release in Laboratory of Allergic Disease 2 (LAD2) cells via Lyn-PLCγ-IP3R-Ca2+ and Lyn-p38/NF-κB signaling pathway. Moreover, ALA (0, 50, 100, and 200 µM) inhibited C48/80 (30 µg/ml)- and SP (4 µg/ml)-induced calcium influx in Mas-related G-protein coupled receptor member X2 (MrgX2)-HEK293 cells and in vitro kinase assays confirmed that ALA inhibited the activity of Lyn kinase. In response to 200 µM of ALA, the activity of Lyn kinase by (7.296 ± 0.03751) × 10-5 units/µl and decreased compared with C48/80 (30 µg/ml) by (8.572 ± 0.1365) ×10-5 units/µl. CONCLUSION: Our results demonstrate that ALA might be a potential Lyn kinase inhibitor, which could be used to treat pseudo-allergic reaction-related diseases such as urticaria.


Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos/farmacologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Ácido alfa-Linoleico/farmacologia , Quinases da Família src/antagonistas & inibidores , Animais , Degranulação Celular/efeitos dos fármacos , Quimiocinas/metabolismo , Relação Dose-Resposta a Droga , Humanos , Imunoglobulina E/imunologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptores Acoplados a Proteínas-G/metabolismo , Receptores de Neuropeptídeos/metabolismo , p-Metoxi-N-metilfenetilamina/toxicidade , Quinases da Família src/química , Quinases da Família src/imunologia , Quinases da Família src/metabolismo
7.
Phytomedicine ; 80: 153340, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33130471

RESUMO

BACKGROUND: Oleanolic acid (OA) is an active compound found in a variety of medicinal herbs and plants. Though OA has been widely attributed with a variety of biological activities, studies focused on its anti-allergic inflammation properties are insufficient. PURPOSE: Given the rapid increase in allergic diseases and the lack of fundamental treatment options, this study aimed to find a safe and effective therapy for allergic disorders. METHODS: We evaluated the inhibitory effect of OA on allergic inflammatory response and the possible mechanisms underlying the effect using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cell (HMC)-1, and a mouse model of compound 48/80-induced anaphylactic shock. RESULTS: OA suppressed pro-inflammatory cytokine expressions in PMACI-induced HMC-1 cells by inhibiting activation of the Akt, p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and signal transducer and activator of transcription (STAT) 1 signaling pathways. Moreover, OA showed a protective effect against compound 48/80-induced anaphylactic shock through inhibition of histamine release and immunoglobulin E level via regulation of NF-κB and STAT1 activation. CONCLUSION: The results showed that OA suppressed mast cell-mediated allergic response by transcriptional regulation. We suggest that OA has potential effect against allergic inflammatory disorders, including anaphylaxis, and might be a useful therapeutic agent for allergic disease.


Assuntos
Anafilaxia/prevenção & controle , Antialérgicos/farmacologia , Mastócitos/efeitos dos fármacos , Ácido Oleanólico/farmacologia , Anafilaxia/induzido quimicamente , Animais , Calcimicina/toxicidade , Linhagem Celular , Citocinas/metabolismo , Liberação de Histamina/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Masculino , Mastócitos/metabolismo , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Ésteres de Forbol/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT1/metabolismo , p-Metoxi-N-metilfenetilamina/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Allergol. immunopatol ; 48(6): 646-653, nov.-dic. 2020. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-199255

RESUMO

INTRODUCTION AND OBJECTIVES: Allergic asthma is a complex chronic disease of the respiratory system presenting with cough, dyspnea, wheezing and airway obstruction. More than 300 million people of all age spectrums suffer from asthma worldwide. Immunological and inflammatory processes are main contributors to asthma. Cytokines produced by T helper 2 lymphocytes play main roles in asthma development and progression. Silymarin, a therapeutic agent with anti-oxidative properties, is a main component of Silybium marinum. We herein aimed to compare the anti-inflammatory and anti-allergic effects of two silymarin isomers, isosilybin A and silydianin, in the treatment of allergic asthma. MATERIALS AND METHODS: After isolating and purifying isosilybin A and silydianin, Balb/c mouse model of allergic asthma was produced using ovalbumin injection. Seventy mice were categorized into five (1 normal and 4 asthmatic) groups (n = 14 per group). Mice in three of four asthmatic groups were treated with either isosilybin A, silydianin or budesonide. The 4th asthmatic group was used as positive control, with the non-asthmatic group serving as negative control. Airway hyperresponsiveness (AHR) and levels of IL-4, IL-5 and IL-13 in the BAL fluid were determined. Gene expressions of IL-4, IL-5, IL-13 and MUC5ac, as well as IgE serum level were also measured. Cellular composition of BAL fluid and lungs histopathology were finally investigated. RESULTS: Isosilybin A and silydianin reduced eosinophilic infiltration of lungs, IL-4 and IL-5 levels in BAL fluid, IL-4 and IL-5 gene expressions, as well as AHR in Balb/c mouse model of asthma. However, no significant changes were observed in IL-13 level and mucus hyper-secretion. CONCLUSION: According to our study, isosilybin A and silydianin can control main symptoms of asthma by modulating immune responses


No disponible


Assuntos
Animais , Feminino , Camundongos , Silimarina/análogos & derivados , Imunomodulação/efeitos dos fármacos , Asma/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Antialérgicos/farmacologia , Camundongos Endogâmicos BALB C , Asma/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/análise , Expressão Gênica , Imunoglobulina E/sangue , Ensaio de Imunoadsorção Enzimática , Resultado do Tratamento , Reprodutibilidade dos Testes
9.
Int Arch Allergy Immunol ; 181(6): 404-416, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32417836

RESUMO

BACKGROUND: The current treatment for allergic rhinitis (AR) is inadequate. OBJECTIVE: The present study aimed to investigate the therapeutic effect of taurine on AR and to identify the underlying molecular mechanisms. METHODS: The serum level of the antioxidant enzyme extracellular superoxide dismutase (SOD3) was determined in AR patients and in healthy controls. The antiallergic inflammatory effects of taurine were evaluated in a dinitrophenyl-human serum albumin (DNP-HSA)-stimulated human mast cell line (HMC-1) and in an ovalbumin (OVA)-induced AR mouse model. RESULTS: Clinically, a reduction in serum level of SOD3 was observed in AR patients. Taurine treatment led to dose-dependent increases in SOD3 at both protein and mRNA levels in HMC-1 cells. SOD3 production was regulated by peroxisome proliferator-activated receptor-γ (PPAR-γ) in response to taurine. SOD3 overexpression inhibited the release of proinflammatory cytokines including tumor necrosis factor-α (, interleukin (IL)-4, and IL-6. Its overexpression also ameliorated the loss of interferon-γ. SOD3 and PPAR-γ influenced inflammatory cytokine production via regulation of the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). An OVA-induced AR animal model study showed that taurine was efficacious in alleviating allergic inflammatory reactions by relieving behavior symptoms of AR mice and reducing eosinophilic and mast cell infiltration into the nasal cavity. In addition, taurine treatment increased the production of SOD3 and PPAR-γ, which, in turn, suppressed expression of proinflammatory cytokines through phosphorylation of ERK1/2. CONCLUSION: Taurine could potentially serve as a therapeutic treatment for allergic disorders.


Assuntos
Antialérgicos/farmacologia , Mastócitos/efeitos dos fármacos , Rinite Alérgica/tratamento farmacológico , Taurina/farmacologia , Adulto , Animais , Antialérgicos/uso terapêutico , Biomarcadores/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , PPAR gama/metabolismo , Rinite Alérgica/sangue , Superóxido Dismutase/sangue , Taurina/uso terapêutico , Resultado do Tratamento
11.
Int J Mol Sci ; 21(4)2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32079131

RESUMO

The review collects together some recent information on the identity and pharmacological properties of magnoflorine, a quaternary aporphine alkaloid, that is widely distributed within the representatives of several botanical families like Berberidaceae, Magnoliaceae, Papaveraceae, or Menispermaceae. Several findings published in the scientific publications mention its application in the treatment of a wide spectrum of diseases including inflammatory ones, allergies, hypertension, osteoporosis, bacterial, viral and fungal infections, and some civilization diseases like cancer, obesity, diabetes, dementia, or depression. The pharmacokinetics and perspectives on its introduction to therapeutic strategies will also be discussed.


Assuntos
Aporfinas/química , Aporfinas/farmacologia , Descoberta de Drogas , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Antialérgicos/química , Antialérgicos/farmacocinética , Antialérgicos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Antidepressivos/química , Antidepressivos/farmacocinética , Antidepressivos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Aporfinas/farmacocinética , Metabolismo dos Carboidratos/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacocinética , Plantas/química
12.
Eur J Pharmacol ; 874: 173020, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32087254

RESUMO

Steroidal agent is a standard clinical treatment of atopic dermatitis; however, have serious side effects. Artesunate is reported to exhibit anti-inflammatory properties although its effect on atopic eczema remains unknown. We investigated the therapeutic effects and possible mechanism of systemic artesunate on DNCB-induced atopic dermatitis in a BALB/c mouse model. To ascertain artesunate (5 and 10 mg/kg) efficacy, skin dermatitis severity and ear, spleen, and lymph node weight were evaluated. Skin tissue mRNA and protein expression and serum cytokine levels were examined. Artesunate significantly improved atopic dermatitis symptoms, decreasing the dermatitis score, ear weight difference, spleen weight, and lymph node weight compared with those following DNCB treatment. Artesunate reduced ear and skin epidermal thickness and mast cell infiltration, as determined using hematoxylin-eosin and toluidine blue staining, respectively. The basal level of IgE (287.67 ± 70.41 ng/ml) and TNF-α (19.94 ± 3.98 pg/ml) were Significantly elevated by DNCB (IgE: 1273.23 ± 176.53 ng/ml; TNF-α: 57.53 ± 3.87 pg/ml), while markedly been suppressed in the treatment group (AS-L: IgE: 1100.25 ± 135.32 ng/ml; TNF-α: 38.47 ± 3.26 pg/ml; AS-H: IgE: 459.46 ± 74.75 ng/ml; TNF-α: 24.38 ± 3.85 pg/ml). Among Th17 cell-related factors, DNCB treatment increased mRNA expression of IL-6, IL-17, IL-23, STAT3, and ROR-γt, but reduced TGF-ß and SOCS 3; While artesunate reverse these changes. Compared with the model group, artesunate promoted SOCS3 protein and significantly inhibited ROR-γt protein and STAT3 phosphorylation. Thus, artesunate attenuates DNCB-induced atopic dermatitis by inhibiting the release of inflammatory cytokines and downregulating Th17 cell responses in atopic dermatitis mice.


Assuntos
Antialérgicos/uso terapêutico , Artesunato/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Células Th17/efeitos dos fármacos , Animais , Antialérgicos/farmacologia , Artesunato/farmacologia , Linhagem Celular , Citocinas/sangue , Citocinas/genética , Citocinas/imunologia , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Dinitroclorobenzeno , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/imunologia , Células Th17/imunologia
13.
Immunopharmacol Immunotoxicol ; 42(2): 74-83, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32041439

RESUMO

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.


Assuntos
Antialérgicos/farmacologia , Brassica/química , Isotiocianatos/farmacologia , Mastócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antialérgicos/isolamento & purificação , Caspase 1/metabolismo , Linhagem Celular , Simulação por Computador , Humanos , Interleucinas/metabolismo , Isotiocianatos/isolamento & purificação , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos/imunologia , NF-kappa B/metabolismo , Extratos Vegetais/isolamento & purificação , Fator de Necrose Tumoral alfa/metabolismo
14.
Molecules ; 25(4)2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32102220

RESUMO

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/metabolismo
15.
Sci Rep ; 10(1): 197, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932619

RESUMO

Translationally controlled tumor protein (TCTP), also called histamine releasing factor, is an evolutionarily conserved multifunctional protein in eukaryotes. We previously reported that extracellular TCTP acquires its cytokine-like function following dimerization. This study aims to identify the functional domain involved in the cytokine-like function of dimerized TCTP (dTCTP). We performed X-ray crystallographic studies and a deletion mutant of dTCTP which lacks the flexible loop domain. Synthetic peptides corresponding to TCTP domains and antibodies developed against them were examined for the anti-allergic effect. In an OVA-induced airway inflammation mouse model, inhibitory effect of synthetic peptides was evaluated. dTCTP was mediated by dimers between Cys172s of TCTP monomers. Synthetic peptides corresponding to the flexible loop and helix 2 domain of TCTP, and antibodies against them inhibited dTCTP-induced IL-8 release. In particular, the TCTP mutant lacking the flexible loop domain decreased the inflammatory cytokine activity of dTCTP. We conclude that the flexible loop and helix 2 domain of TCTP are the functional domains of dTCTP. They may have the potential to be therapeutic targets in the suppression of allergic reactions induced by dTCTP.


Assuntos
Antialérgicos/farmacologia , Biomarcadores Tumorais/química , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Ovalbumina/toxicidade , Fragmentos de Peptídeos/farmacologia , Animais , Biomarcadores Tumorais/metabolismo , Cristalografia por Raios X , Citocinas/metabolismo , Feminino , Hipersensibilidade , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Endogâmicos BALB C , Domínios Proteicos , Multimerização Proteica , Transdução de Sinais
16.
Molecules ; 25(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979346

RESUMO

Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Several biological activities have been attributed to gedunin, including antibacterial, insecticidal, antimalarial, antiallergic, anti-inflammatory, anticancer, and neuroprotective effects. The discovery of gedunin as a heat shock protein (Hsp) inhibitor represented a very important landmark for its application as a biological therapeutic agent. The current study is a critical literature review based on the several biological activities so far described for gedunin, its therapeutic effect on some human diseases, and future directions of research for this natural compound.


Assuntos
Antineoplásicos/farmacologia , Limoninas/farmacologia , Meliaceae/química , Animais , Antialérgicos/química , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antiparasitários/química , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Limoninas/química , Limoninas/toxicidade , Meliaceae/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Sementes/química , Sementes/metabolismo
17.
Carbohydr Polym ; 230: 115567, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887913

RESUMO

Sulfated oligosaccharide of Gracilaria lemaneiformis (GLSO) was prepared from sulfated polysaccharides which possessed antiallergic activity by degradation with high temperature and pressure combined with vitamin C treatment. The present study demonstrated that GLSO could attenuate food anaphylaxis, and inhibit the production of immunoglobulin E, histamine, and related cytokines in both prevention and therapy ovalbumin-induced mice model. Additionally, the gut microbiota analysis revealed that GLSO markedly rescued OVA-induced changes in the Firmicutes to Bacteroidetes ratio. Following flow cytometry, GLSO was found to suppress the subpopulation of T helper 2 and B cells, and significantly up-regulate regulatory T cells (Tregs) differentiation. Furthermore, GLSO-mediated immunosuppression could be verified by co-culturing Tregs sorted from GLSO-treated mice and CD4+ T cells or mast cells. In a word, GLSO attenuated food anaphylaxis through the regulation of gut microbiota and induction of immunosuppression. GLSO had the potential to be used as a nutrient component against food allergy.


Assuntos
Antialérgicos/farmacologia , Hipersensibilidade Alimentar/tratamento farmacológico , Gracilaria/química , Oligossacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antialérgicos/química , Citocinas/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/prevenção & controle , Humanos , Imunossupressão , Mastócitos/efeitos dos fármacos , Camundongos , Oligossacarídeos/química , Oligossacarídeos/imunologia , Substâncias Protetoras/química , Sulfatos/química , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
18.
Mol Immunol ; 118: 201-209, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896496

RESUMO

Trigonelline, one of the alkaloids contained in coffee, is important not only as one of the constituents of aroma and flavor in coffee but also as a useful source of nutrition. Its anti-microbial, anti-carcinogenic, and anti-hyperglycemic effects have been investigated in previous studies. However, there have not been any studies examining the anti-degranulation effect of trigonelline. In this study, the anti-degranulation effect of trigonelline was evaluated in in vitro and in vivo models using a rat basophilic leukemia cell line, RBL-2H3 cells, and a passive cutaneous anaphylaxis (PCA) reaction in mice, respectively. In the ß-hexosaminidase release assay, trigonelline effectively suppressed antigen-induced degranulation of RBL-2H3 cells in a dose-dependent manner without cytotoxicity. Trigonelline also inhibited FcεRI-mediated intracellular signaling pathways, such as phosphorylation of PLCγ1, PI3 K, and Akt, in antigen-stimulated RBL-2H3 cells and suppressed the PCA response in mice. Moreover, trigonelline also inhibited the microtubule formation in RBL-2H3 cells, indicating that trigonelline could inhibit IgE-sensitized mast cell degranulation by attenuating both the intracellular calcium-dependent and independent pathways. These results revealed that trigonelline possesses the anti-degranulation effect against the development of allergic diseases.


Assuntos
Alcaloides/farmacologia , Degranulação Celular/efeitos dos fármacos , Animais , Antialérgicos/farmacologia , Cálcio/metabolismo , Linhagem Celular Tumoral , Feminino , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/metabolismo , Imunoglobulina E/metabolismo , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos
19.
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
20.
Muscle Nerve ; 61(3): 408-415, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31883124

RESUMO

INTRODUCTION: In this study we aimed to clarify the association between interleukin-6 (IL-6) secretion in fibroblasts in carpal tunnel syndrome (CTS) patients and their biophysical parameters, including association with trigger finger and whether tranilast inhibits IL-6 secretion in fibroblasts. METHODS: Fibroblasts were obtained from tenosynovial tissue harvested from idiopathic CTS patients undergoing carpal tunnel release and tenosynovectomy and cultured in media containing tranilast with or without tumor necrosis-α (TNF-α) or interleukin-1ß (IL-1ß). Their proliferation was evaluated and secreted IL-6 levels and IL-6 mRNA expression were quantified. Correlations between IL-6 concentration and patient characteristics were examined. RESULTS: IL-6 secretion was significantly associated with trigger finger (P = .001). Tranilast inhibited fibroblast proliferation in a dose-dependent manner and suppressed IL-6 secretion. DISCUSSION: IL-6 overproduction in tenosynovial tissue may account for the association between CTS and trigger finger. Future studies should investigate whether tranilast can be used to treat patients with CTS.


Assuntos
Antialérgicos/farmacologia , Síndrome do Túnel Carpal/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Interleucina-6/metabolismo , Dedo em Gatilho/metabolismo , ortoaminobenzoatos/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Síndrome do Túnel Carpal/complicações , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Dedo em Gatilho/complicações , Dedo em Gatilho/diagnóstico
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