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1.
Curr Pharm Biotechnol ; 22(1): 159-167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32216736

RESUMO

BACKGROUND: Tripterine (TRI), an active monomer in Tripterygium wilfordii, has significant pharmacological activities, such as anti-inflammatory, immunosuppressive and anti-tumor activities. TRI may be used to treat allergic diseases because of its characteristics of immunosuppression. OBJECTIVE: This study aims to explore the anti-allergic effect of TRI. METHODS: It was tested in vivo and in vitro in this study. RESULTS: The results showed that TRI could significantly inhibit histamine release from rat peritoneal mast cells; the inhibitory effect of TRI on histamine release was stronger than that of other known histamine inhibitors such as disodium cromoglyceride. TRI also significantly inhibited systemic anaphylactic shock induced by compound 48/80 and skin allergy induced by IgE, and inhibited the expression of inflammatory factors secreted by Human Mast Cells (HMC-1) induced by Phorbol 12-Myristate 13- Acetate (PMA) and calcium carrier A23187. In the animal model of allergic rhinitis induced by Ovalbumin (OA), the scores of friction, histamine, IgE, inflammatory factors and inflammatory cells decreased after TRI was administered orally or nasally. CONCLUSION: TRI, as an active immunoregulatory factor, has great potential in the treatment of mast cell-mediated allergic diseases.


Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos/farmacologia , Liberação de Histamina/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Rinite Alérgica/tratamento farmacológico , Triterpenos/farmacologia , Animais , Antialérgicos/uso terapêutico , Calcimicina/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Masculino , Mastócitos/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Triterpenos Pentacíclicos , Ratos , Rinite Alérgica/imunologia , Acetato de Tetradecanoilforbol/farmacologia , Triterpenos/uso terapêutico , p-Metoxi-N-metilfenetilamina/farmacologia
2.
Molecules ; 25(17)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887288

RESUMO

In the present study the effects and molecular mechanisms of wheat bran (WB), the hard outer layer of the wheat kernel used in food ingredients, on mast cell-mediated allergic responses in vitro and in vivo were investigated. The water extract of WB inhibited degranulation and expression of allergic and inflammatory mediators such as tumor necrosis factor-α, cyclooxygenase-2 and inducible nitric oxide synthase in antigen-stimulated RBL-2H3 cells. These anti-allergic activities of WB were mediated by the inactivation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, which play important roles in degranulation and expression of various allergic and inflammatory molecules. In agreement with its in vitro effects, WB inhibited immunoglobulin E (IgE)/antigen-induced and compound 48/80-induced anaphylactic reactions in vivo. Taken together, these findings suggest the pharmacological potential of WB in the regulation of allergic diseases, including allergic rhinitis, atopic dermatitis, asthma and anaphylaxis.


Assuntos
Fibras na Dieta/farmacologia , Hipersensibilidade/patologia , Mastócitos/patologia , Extratos Vegetais/farmacologia , Animais , Antígenos/imunologia , Degranulação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Imunoglobulina E/metabolismo , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Mastócitos/fisiologia , Camundongos Endogâmicos BALB C , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , beta-N-Acetil-Hexosaminidases/metabolismo , p-Metoxi-N-metilfenetilamina/farmacologia
3.
Pharmacol Res Perspect ; 7(6): e00547, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31832205

RESUMO

Activation of MrgX2, an orphan G protein-coupled receptor expressed on mast cells, leads to degranulation and histamine release. Human MrgX2 binds promiscuously to structurally diverse peptides and small molecules that tend to have basic properties (basic secretagogues), resulting in acute histamine-like adverse drug reactions of injected therapeutic agents. We set out to identify MrgX2 orthologues from other mammalian species used in nonclinical stages of drug development. Previously, the only known orthologue of human MrgX2 was from mouse, encoded by Mrgprb2. MrgX2 genes of rat, dog (beagle), minipig, pig, and Rhesus and cynomolgus monkey were identified by bioinformatic approaches and verified by their ability to mediate calcium mobilization in transfected cells in response to the classical MrgX2 agonist, compound 48/80. The peptide GSK3212448 is an inhibitor of the PRC2 epigenetic regulator that caused profound anaphylactoid reactions upon intravenous infusion to rat. We showed GSK3212448 to be a potent MrgX2 agonist particularly at rat MrgX2. We screened sets of drug-like molecules and peptides to confirm the highly promiscuous nature of MrgX2. Approximately 20% of drug-like molecules activated MrgX2 (pEC50 ranging from 4.5 to 6), with the principle determinant being basicity. All peptides tested of net charge +3 or greater exhibited agonist activity, including the cell penetrating peptides polyarginine (acetyl-Arg9-amide) and TAT (49-60), a fragment of HIV-1 TAT protein. Finally, we showed that the glycopeptide antibiotic vancomycin, which is associated with clinical pseudo-allergic reactions known as red man syndrome, is an agonist of MrgX2.


Assuntos
Anafilaxia/induzido quimicamente , Mastócitos/efeitos dos fármacos , Proteínas do Tecido Nervoso/agonistas , Fragmentos de Peptídeos/efeitos adversos , Receptores Acoplados a Proteínas G/agonistas , Receptores de Neuropeptídeos/agonistas , Vancomicina/efeitos adversos , Anafilaxia/imunologia , Animais , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Linhagem Celular Tumoral , Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/efeitos adversos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/efeitos adversos , Células HEK293 , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Humanos , Mastócitos/imunologia , Mastócitos/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/imunologia , Proteínas do Tecido Nervoso/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/imunologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/imunologia , Receptores de Neuropeptídeos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Síndrome , Vancomicina/administração & dosagem , p-Metoxi-N-metilfenetilamina/farmacologia
4.
Planta Med ; 84(1): 26-33, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28662529

RESUMO

According to modern ethnobotanical records, the fruit of Hippophae rhamnoides is effective in the treatment of different allergic symptoms. In order to obtain pharmacological evidence for this observation, the fruit was investigated for anti-inflammatory activity using in vivo animal models. Aqueous and 70% MeOH extracts were tested in 48/80-induced rat paw edema assay after oral administration, and it was found that the 70% MeOH extract (500 mg/kg) reduced significantly edema volume (0.660 ± 0.082 mL vs. control 0.935 ± 0.041 mL). Extracts of different parts of the fruit (pulp, peel, seed) were investigated in the same assay, and the peel extract was shown to exhibit maximum edema-reducing effect (0.470 ± 0.124 mL vs. control 0.920 ± 0.111 mL). This extract was used to elucidate the mode of action. Different inflammation inducers (serotonin, histamine, dextran, bradykinin, and carrageenan) were applied in the rat paw model, but the extract inhibited only the compound 48/80 elicited inflammation. The active extract was then fractionated by solvent-solvent partitioning and chromatographic methods with the guidance of the 48/80-induced anti-inflammatory assay, and the main compounds responsible for the activity were identified as ursolic acid and oleanolic acid. Our data suggest that the activity is most probably based on a membrane stabilizing effect caused by the inhibition of degranulation of mast cells. Moreover, previously unknown 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans, nectandrin B, fragransin A2, and saucernetindiol were isolated and identified from H. rhamnoides for the first time.


Assuntos
Anti-Inflamatórios/farmacologia , Frutas/química , Hippophae/química , Extratos Vegetais/farmacologia , Animais , Edema/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , p-Metoxi-N-metilfenetilamina/farmacologia
5.
Physiol Int ; 104(1): 15-24, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28361577

RESUMO

In this study, we aimed to investigate the effects of Nigella sativa seeds and certain species of fungi extracts on the number and degranulation states of dural mast cells in rats. Rats were fed ad libitum with normal tap water or tap water with extract of N. sativa seed, Ramaria condensata, Lactarius salmonicolor, Lactarius piperatus, and Tricholoma terreum for 3 days. Mast cells in dura mater were counted and evaluated in terms of granulation and degranulation states. Compound 48/80, a mast cell degranulating agent, and T. terreum significantly increased the percent of degranulated mast cells in dura mater, respectively (p < 0.01 and p < 0.05). Moreover, T. terreum causes a significant increase in the total number of mast cells (p < 0.05). N. sativa significantly inhibited mast cell degranulation induced by both the compound 48/80 and T. terreum (p < 0.05), and significantly decreased the mast cell numbers increased by T. terreum (p < 0.05). Our results suggested that T. terreum following ingestion can contribute to headaches like migraine via dural mast cell degranulation and N. sativa may be able to exert analgesic and anti-inflammatory effects by stabilizing dural mast cells. However, investigation is needed to determine the ingredients of N. sativa that may be responsible for these beneficial effects.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Degranulação Celular/efeitos dos fármacos , Fungos/química , Mastócitos/efeitos dos fármacos , Nigella sativa/química , Extratos Vegetais/farmacologia , Sementes/química , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Dura-Máter/citologia , Masculino , Mastócitos/imunologia , Mastócitos/microbiologia , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos Wistar , Tricholoma/química , p-Metoxi-N-metilfenetilamina/farmacologia
6.
J Ethnopharmacol ; 153(3): 541-51, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24556221

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pistacia integerrima J.L. Stewart ex Brandis locally known as Karkatashringi is an important medicinal plant whose galls are valued in traditional medicine used in India for the treatment of asthma, chronic bronchitis, phthisis, diarrhea, fever, other ailments for the respiratory tract, and as antispasmodic, carminative, antiamoebic and anthelmintic. However, in vitro and in vivo investigations providing new insights into its pharmacological properties have not been thoroughly investigated yet. The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). METHODS: EOPI was tested using in vitro studies such as antioxidant activity, mast cell degranulation, angiogenesis, isolated guinea pig ileum preparation and soyabean lipoxidase enzyme activity. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. RESULTS: EOPI (5-30 µg/ml) inhibits 5-lipoxidase enzyme activity with IC50 of 19.71 µg/ml and DPPH scavenging activity up to 100 µg/ml with maximum inhibition of 44.93 ± 2.53% at 100 µg/ml. Pre-treatment with EOPI inhibited erythropoietin-induced angiogenesis. It showed dose dependent (10, 30 and 100 µg/ml) anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation to an extent 19.08 ± 0.47%. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggests that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30mg/kg i.p.) inhibited lipopolysaccharide-induced increase in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Roflumilast was used as a standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. CONCLUSION: The study demonstrates the effectiveness of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.


Assuntos
Inibidores da Angiogênese/farmacologia , Antiasmáticos/farmacologia , Antioxidantes/farmacologia , Inibidores de Lipoxigenase/farmacologia , Óleos Voláteis/farmacologia , Pistacia , Alérgenos , Inibidores da Angiogênese/uso terapêutico , Animais , Antiasmáticos/uso terapêutico , Antioxidantes/uso terapêutico , Araquidonato 5-Lipoxigenase/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , Broncoconstrição/efeitos dos fármacos , Contagem de Células , Feminino , Cobaias , Liberação de Histamina/efeitos dos fármacos , Íleo/efeitos dos fármacos , Íleo/fisiologia , Lipopolissacarídeos , Inibidores de Lipoxigenase/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Contração Muscular/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Óleos Voláteis/uso terapêutico , Ovalbumina , Peroxidase/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Pneumonia/patologia , Ratos Sprague-Dawley , Zigoto/efeitos dos fármacos , Zigoto/fisiologia , p-Metoxi-N-metilfenetilamina/farmacologia
7.
Pharm Biol ; 52(7): 804-13, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24405177

RESUMO

CONTEXT: Woodfordia fruticosa Kurz. (Lythraceae) flowers are ethnopharmacologically acclaimed in the Indian medicinal system to treat asthma. OBJECTIVE: To evaluate W. fruticosa flower extracts for anti-asthmatic effect. MATERIALS AND METHODS: Ethyl acetate, acetone, methanol, and hydro-alcohol extracts of W. fruticosa flowers were obtained successively and standardized. Ability of extracts to stabilize free radicals and compound-48/80-induced mast cell degranulation was evaluated. In vitro anti-inflammatory potential of extracts at 100 and 200 µg/ml by membrane stabilization and in vivo inhibition of rat paw edema up to 5 h (100 and 200 mg/ml; p.o.) was evaluated. In vitro bronchorelaxant effect was examined against histamine- and acetylcholine (1 µg/ml; independently)-induced guinea pig tracheal contraction. Extracts were evaluated for bronchoprotection (in vivo) ability against 0.1% histamine- and 2% acetylcholine-induced bronchospasm in guinea pigs at 100 and 200 mg/ml; p.o. RESULTS: Standardization studies revealed that the methanol extract exhibited highest polyphenolic (62.66 GAE), and flavonoid (6.32 RE) content and HPLC fingerprinting confirmed the presence of gallic acid (Rt 1.383). IC50 values for DPPH scavenging and metal chelation by the methanol extract were 40.42 and 31.50 µg/ml. Methanol and ethyl acetate extracts at 100 µg/ml exhibited 06.52 and 07.12% of histamine release. Methanol, ethyl acetate, and hydro alcohol extracts at 200 mg/kg demonstrated 32.73, 29.83, 26.75% and 32.46, 9.38, 26.75% inhibition of egg albumin and carrageenan-induced inflammation, respectively. Methanol extract exhibited 100% bronchorelaxation and 48.83% bronchoprotection. CONCLUSION: Woodfordia fruticosa flower (WFF) extracts exhibited anti-asthmatic effect by demonstrating bronchoprotection, bronchorelaxation, anti-inflammatory, antioxidant, and mast cell stabilization ability.


Assuntos
Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Flores/química , Mastócitos/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Woodfordia/química , Acetilcolina/farmacologia , Animais , Antioxidantes/farmacologia , Broncodilatadores/farmacologia , Edema/tratamento farmacológico , Cobaias , Histamina/metabolismo , Histamina/farmacologia , Mastócitos/metabolismo , Extratos Vegetais/uso terapêutico , Ratos , Solventes/química , Traqueia/efeitos dos fármacos , p-Metoxi-N-metilfenetilamina/farmacologia
8.
Exp Toxicol Pathol ; 65(4): 419-26, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22261360

RESUMO

BACKGROUND: We investigated the effect of Anemarrhena asphodeloides Bunge (Liliaceae) water extract (AAWE) on mast cell-mediated anaphylactic reactions. Mast cell-mediated anaphylactic reaction is involved in many allergic diseases, including asthma and allergic rhinitis. In Korea, where it has been used as a traditional medicine, AAWE is known to have antioxidant and anticancer activity. However, its specific effect on mast cell-mediated anaphylactic reactions is still unknown. METHODS: We examined whether or not AAWE could inhibit IgE-mediated passive cutaneous anaphylaxis (PCA), compound 48/80-induced systemic anaphylaxis, and mast cell activation. RESULTS: Oral administration of AAWE inhibited compound 48/80-induced systemic anaphylaxis in mice. AAWE also inhibited the local allergic reaction, PCA, activated by anti-dinitrophenyl IgE antibody in rats. AAWE reduced compound 48/80-induced degranulation of rat peritoneal mast cells (RPMCs). Moreover, AAWE inhibited histamine release and calcium uptake of RPMCs induced by compound 48/80 in a dose-dependent manner. AAWE also significantly inhibited secretion of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in phorbol 12-myristate 13-acetate plus calcium ionophores A23187-stimulated RPMCs. CONCLUSIONS: These results suggest that AAWE suppresses compound 48/80-induced mast cell activation by inhibition of cellular mechanisms in signaling pathways, and would be beneficial for treatment of mast cell-mediated anaphylactic response.


Assuntos
Anafilaxia/imunologia , Medicamentos de Ervas Chinesas/farmacologia , Mastócitos/efeitos dos fármacos , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Fitoterapia/métodos , Anemarrhena/química , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Liberação de Histamina/efeitos dos fármacos , Imunoglobulina E , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , p-Metoxi-N-metilfenetilamina/imunologia , p-Metoxi-N-metilfenetilamina/farmacologia
9.
Life Sci ; 91(1-2): 20-8, 2012 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-22683427

RESUMO

AIMS: Betula platyphylla (B. platyphylla) has traditionally been used in Korea to treat inflammatory diseases. However, the exact mechanism that accounts for the anti-inflammatory effect of B. platyphylla is not completely understood. The aim of the present study is to elucidate whether and how B. platyphylla modulates the mast cell-mediated allergy inflammation in vitro and in vivo. MAIN METHODS: We investigated to ascertain the pharmacological effects of B. platyphylla on both compound 48/80 or histamine-induced scratching behaviors and 2, 4-dinitrochlrobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of B. platyphylla, we evaluated the effects of B. platyphylla on the release of histamine in compound 48/80-induced rat peritoneal mast cells (RPMCs), production of inflammatory mediators and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). KEY FINDINGS: The finding of this study demonstrated that B. platyphylla reduced compound 48/80 or histamine-induced scratching behaviors and DNFB-induced atopic dermatitis in mice. Additionally, B. platyphylla inhibited the release of histamine in RPMC and production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. SIGNIFICANCE: Collectively, the findings of this study provide us with novel insights into the pharmacological actions of B. platyphylla as a potential molecule for use in the treatment of allergic inflammatory diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Betula/química , Dermatite Atópica/tratamento farmacológico , Mastócitos/imunologia , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Western Blotting , Linhagem Celular , Dermatite Atópica/induzido quimicamente , Humanos , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Ratos , República da Coreia , p-Metoxi-N-metilfenetilamina/farmacologia
10.
Zhong Xi Yi Jie He Xue Bao ; 10(6): 690-4, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22704419

RESUMO

OBJECTIVE: Present study was aimed to evaluate the protective effect of Bresol®, a polyherbal formulation, on mast cell degranulation and histamine release from mast cells. METHODS: Mast cell-stabilizing activity of Bresol® was evaluated against compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells in ex vivo conditions. RESULTS: Microscopy of the control group smears showed more of intact mast cells, with very minimum number of degranulated mast cells and negligible amount of histamine release. In contrast, incubation of mast cells with compound 48/80 caused significant degranulation of the mast cells associated with release of high concentration of histamine in the positive control group. Furthermore, Bresol® at 100 mg/L showed a significant inhibition of compound 48/80-induced mast cell degranulation. In addition, Bresol® significantly and dose-dependently inhibited compound 48/80-induced histamine release. CONCLUSION: Bresol® inhibits compound 48/80-induced mast cell degranulation and histamine release in ex vivo conditions. The present findings could be one of the non-immunological mechanism responsible for usefulness of Bresol® in various allergic conditions.


Assuntos
Liberação de Histamina/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Preparações de Plantas/farmacologia , p-Metoxi-N-metilfenetilamina/farmacologia , Animais , Degranulação Celular/efeitos dos fármacos , Exocitose/efeitos dos fármacos , Ratos , Ratos Wistar
11.
J Ethnopharmacol ; 141(1): 345-9, 2012 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-22414480

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis (SB) is one of the most widely used medicinal herbs for the treatment of inflammation. In this study, we investigated the antiallergic effect of SB in vivo and in vitro. MATERIALS AND METHODS: Sprague-Dawley (SD) rats received intradermal injections of anti-DNP IgE at each of three dorsal skin sites. Forty-eight hours later, each rat received an injection of DNP-HSA in saline containing 4% Evans blue through the dorsal vein of the penis. One hour before injection, SB extract was administered orally. The dorsal skin of the rats was removed and the pigment area measured. In addition, rat peritoneal mast cells (RPMCs) were cultured and purified to investigate histamine release. In vitro, human mast cells (HMC-1) were pretreated with SB extract for 30min before stimulation with phorbol 12-myristate 13-acetate (PMA) plus A23187. The effects on pro-inflammatory cytokine expression and mitogen activated protein (MAP) kinase expression were investigated using TNF-α and IL-8 assays, and Western blotting analysis of HMC-1 cells. RESULTS AND CONCLUSIONS: SB treatment inhibited the passive cutaneous anaphylaxis reaction compared to the control group, and histamine release decreased significantly following treatment of RPMCs with SB. In HMC-1 cells, SB restored IL-8 and TNF-α expression and inhibited MAP kinase expression in compound 48/80-induced HMC-1 cells. These data suggest that SB may prove to be a useful anti-inflammatory agent through its downregulation of the expression of various inflammatory mediators.


Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Dermatite Alérgica de Contato/prevenção & controle , Extratos Vegetais/farmacologia , Scutellaria baicalensis , Administração Oral , Animais , Antialérgicos/administração & dosagem , Antialérgicos/isolamento & purificação , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Western Blotting , Calcimicina/farmacologia , Ionóforos de Cálcio/farmacologia , Células Cultivadas , Dermatite Alérgica de Contato/imunologia , Dinitrofenóis , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ativação Enzimática , Feminino , Haptenos , Liberação de Histamina/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-8/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Scutellaria baicalensis/química , Albumina Sérica , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/farmacologia
12.
Asian Pac J Trop Med ; 5(3): 180-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22305781

RESUMO

OBJECTIVE: To evaluate the effect of ethylacetate fraction (Fr-Et) and methanolic fraction (Fr-Me) obtained from Cressa cretica L.(C. cretica) L. on experimental models for bronchodilatory activity and mast cell stabilising activity. METHODS: The effect of Fr-Et and Fr-Me were studied on acetylcholine and histamine aerosol-induced broncospasm using guinea pigs as experimental animals. Also, the effects of these fractions were evaluated on the isolated guinea pig tracheal preparations. Besides this mast cell degranulation effect was assessed using egg albumin and compound 48/80 on rat peritoneal mast cells. RESULTS: Significant increase in preconvulsion time was observed due to pretreatment with the fractions when guinea pigs were exposed to histamine and acetylcholine aerosol. Fr-Et and Fr-Me significantly increased the preconvulsion in a dose depended manner that suggestive of bronchodilating activity. Fr-Et and Fr-Me exhibited a significant concentration dependant relaxant effect on guinea pig trachea pre-contracted with CCh, K(+) and histamine. The results revealed that Fr-Et to be more potent than Fr-Me in relaxing histamine and K(+) and calcium induced contraction than CCh induced contractions. Studies on the fractions in protecting mast cell degranulation, which were elicited by the egg albumin as well as synthetic compound 48/80 revealed both the fractions significantly protect the mast cell degranulation, which release mediators such as histamine and proinflammatory cytokines through various stimuli in a dose depended manner. CONCLUSIONS: Thus our study established the bronchodilator activity, and mast cell stabilizing activity which are important mediators that provoke or sustain in asthma.


Assuntos
Espasmo Brônquico/tratamento farmacológico , Broncodilatadores/farmacologia , Convolvulaceae/química , Fitoterapia , Extratos Vegetais/farmacologia , Acetatos/farmacologia , Albuminas/farmacologia , Animais , Cobaias , Mastócitos/efeitos dos fármacos , Metanol/farmacologia , Ratos , Traqueia/efeitos dos fármacos , p-Metoxi-N-metilfenetilamina/farmacologia
13.
Biosci Biotechnol Biochem ; 75(8): 1440-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21821956

RESUMO

Fritillaria ussuriensis (FU, derived from the bulbs of various species of the genus Fritillaria, including Fritillaria thunbergii Miq.) is used in herbal medicine to treat conditions such as eczema, skin burns, and frostbite. In this study, we investigated the mechanism of the anti-allergy effect of FU. FU extract (80 mg/kg), orally administered to Sprague-Dawley (SD) rats, significantly inhibited the passive cutaneous anaphylaxis (PCA) reaction. It inhibited the compound 48/80-induced release of histamine from rat peritoneal mast cells in a concentration-dependent manner. Significant inhibitory effects of the FU extract on IL-6, IL-8, and TNF-α (1, 10, and 100 µg/mL) were observed in HMC-1 cells. Treatment with FU attenuated PMA plus A23187-induced phosphorylation of all three MAPKs, especially at concentrations of 10 and 100 µg/mL. Further, it (80 mg/kg) led to significant inhibition of mast-cell accumulation in ear tissue at the chronic phase. These results indicate that it inhibits allergic reactions.


Assuntos
Antialérgicos/farmacologia , Fritillaria/química , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/tratamento farmacológico , Inflamação/tratamento farmacológico , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Administração Oral , Animais , Antialérgicos/química , Antialérgicos/uso terapêutico , Calcimicina/farmacologia , Liberação de Histamina/imunologia , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Hipersensibilidade/fisiopatologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Masculino , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Anafilaxia Cutânea Passiva/imunologia , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Acetato de Tetradecanoilforbol/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , p-Metoxi-N-metilfenetilamina/farmacologia
14.
Exp Biol Med (Maywood) ; 236(9): 1070-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21807818

RESUMO

Mast cell-mediated allergic reaction is involved in many diseases such as asthma and allergic rhinitis. Therefore, discovery of drugs for the prevention or treatment of allergic disease is an important topic in human health. In this study, we evaluated the effects of water extract of Elsholtzia ciliata (Thunb.) Hyland (Labiatae) (WEEC) on mast cell-mediated allergic inflammation and studied the possible mechanisms of action. WEEC inhibited compound 48/80-induced systemic and immunoglobulin E-mediated local anaphylaxis, and serum histamine release in mice. WEEC reduced intracellular calcium levels and downstream histamine release from human mast cells (HMC-1) activated with phorbol 12-myristate 13-acetate and calcium ionophore A23187. In addition, WEEC decreased gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1ß and IL-6 in HMC-1. The inhibitory effect of WEEC on cytokine expression was nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) dependent. Our results indicate that WEEC inhibits mast cell-mediated allergic inflammatory reactions by suppressing histamine release and proinflammatory cytokine expression, and involvement of calcium, NF-κB and p38 MAPK in these effects.


Assuntos
Cálcio/fisiologia , Hipersensibilidade/tratamento farmacológico , Lamiaceae , Mastócitos/efeitos dos fármacos , NF-kappa B/fisiologia , Extratos Vegetais/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Animais , Cálcio/sangue , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/fisiopatologia , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Masculino , Mastócitos/fisiologia , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/efeitos dos fármacos , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , p-Metoxi-N-metilfenetilamina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos
15.
Pak J Pharm Sci ; 24(3): 359-67, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21715270

RESUMO

Aegeline or N-[2-hydroxy-2(4-methoxyphenyl) ethyl]-3-phenyl-2-propenamide is a main alkaloid isolated from Aegle marmelos Correa collected in Yogyakarta Indonesia. In our study, we investigated the effects of aegeline on the histamine release from mast cell. The study was performed by using (1) rat basophilic leukemia (RBL-2H3) cell line, and (2) rat peritoneal mast cells (RPMCs). DNP(24)-BSA, thapsigargin, ionomycin, compound 48/80 and PMA were used as inducers for histamine release from mast cell. In our study, aegeline inhibited the histamine release from RBL-2H3 cells induced by DNP(24)-BSA. Indeed, aegeline showed strong inhibition when RBL-2H3 cells induced by Ca(2+) stimulants such as thapsigargin and ionomycin. Aegeline is suggested to influence the intracellular Ca(2+) pool only since could not inhibit the (45)Ca(2+) influx into RBL-2H3 cells. Aegeline showed weak inhibitory effects on the histamine release from RPMCs, even though still succeed to inhibit when the histamine release induced by thapsigargin. These findings indicate that aegeline altered the signaling pathway related to the intracellular Ca(2+) pool in which thapsigargin acts. Based on the results, the inhibitory effects of aegeline on the histamine release from mast cells depended on the type of mast cell and also involved some mechanisms related to intracellular Ca(2+) signaling events via the same target of the action of thapsigargin or downstream process of intracellular Ca(2+) signaling in mast cells.


Assuntos
Aegle/química , Amidas/farmacologia , Interações Ervas-Drogas , Liberação de Histamina/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Amidas/isolamento & purificação , Animais , Cálcio/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Dinitrofenóis/antagonistas & inibidores , Dinitrofenóis/farmacologia , Ionomicina/antagonistas & inibidores , Ionomicina/farmacologia , Masculino , Mastócitos/metabolismo , Ratos , Ratos Wistar , Soroalbumina Bovina/antagonistas & inibidores , Soroalbumina Bovina/farmacologia , Acetato de Tetradecanoilforbol/antagonistas & inibidores , Acetato de Tetradecanoilforbol/farmacologia , Tapsigargina/antagonistas & inibidores , Tapsigargina/farmacologia , p-Metoxi-N-metilfenetilamina/antagonistas & inibidores , p-Metoxi-N-metilfenetilamina/farmacologia
16.
Food Chem Toxicol ; 48(10): 2797-802, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20633593

RESUMO

Mast cell-mediated allergic symptoms are involved in many diseases, such as asthma and sinusitis. In this study, we investigated the effect of ethanol extract of fruits of Prunus persica (L) Batsch (FPP) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. FPP dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated local allergic reactions. Histamine releasing from mast cells was reduced by FPP, which was mediated by modulation of intracellular calcium. In addition, FPP attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of FPP on pro-inflammatory cytokines was nuclear factor (NF)-kappaB dependent. Our findings provide evidence that FPP inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-kappaB in these effects.


Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , NF-kappa B/metabolismo , Prunus/química , Anafilaxia/imunologia , Anafilaxia/prevenção & controle , Animais , Western Blotting , Cálcio/metabolismo , Citocinas/biossíntese , Liberação de Histamina/efeitos dos fármacos , Indicadores e Reagentes , Interleucina-8/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Extratos Vegetais/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/farmacologia
17.
J Nat Prod ; 73(7): 1203-6, 2010 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-20586436

RESUMO

Four new chromane derivatives, anthopogochromane (1), anthopogochromene A (2), anthopogochromene B (3), and anthopogochromene C (4), and two known compounds, daurichromenic acid (5) and ilicicolinic acid B (6), have been isolated from the Chinese medicinal plant Rhododendron anthopogonoides. The S absolute configuration of the stereogenic carbons in the chromane and chromene rings of 1-4 was determined from their circular dichroism spectra. Compounds 1 and 2 inhibited compound 48/80-induced histamine release from rat peritoneal mast cells.


Assuntos
Cromanos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Liberação de Histamina/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Plantas Medicinais/química , Rhododendron/química , Animais , Cromanos/química , Cromanos/farmacologia , Dicroísmo Circular , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Estrutura Molecular , Ratos , Estereoisomerismo , p-Metoxi-N-metilfenetilamina/farmacologia
18.
J Ethnopharmacol ; 126(3): 434-6, 2009 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-19781614

RESUMO

AIM OF THE STUDY: To investigate the mast cell stabilization and antihistaminic activities of the rhizomes of Curculigo orchioides (COR). Extract of Curculigo orchioides Gaertn. (Fam. Amaryllidaceae) has been reported to possess immunostimulant, and anti-inflammatory potentials. In Indian traditional system of medicine it is also used as anti-asthmatic and anti-inflammatory. MATERIALS AND METHODS: Estimation of histamine release is key parameter for evaluating any target for its anti-allergic potential. The stabilization potential of the alcoholic extract of COR (100-400mg/kg) against mast cell degranulation was studied on isolated mice peritoneal mast cells. The antihistaminic activity was performed by determining the mortality rate of mice upon exposure to compound 48/80 and effect on inhibition of histamine release upon degranulation. RESULTS: The raised number of intact mast cells intimates that the COR stabilized the mast cell degranulation (60.96+/-1.96%) and percentage antihistaminic potential of the extract (63.58+/-1.8 inhibition at dose of 400mg/kg) and it virtues further work towards the isolation of phytoconstituents from this plant. CONCLUSION: This finding provides evidence that COR inhibits mast cell-derived immediate-type allergic reactions and mast cell degranulation.


Assuntos
Curculigo/química , Antagonistas dos Receptores Histamínicos/farmacologia , Mastócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Degranulação Celular/efeitos dos fármacos , Liberação de Histamina/efeitos dos fármacos , Masculino , Mastócitos/metabolismo , Camundongos , p-Metoxi-N-metilfenetilamina/farmacologia
19.
Arch Pharm Res ; 32(6): 823-30, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19557358

RESUMO

Rosa rugosa is a species of rose native to eastern Asia. The root of R. rugosa has been used to treat diabetes mellitus, pain and chronic inflammatory disease, and a R. rugosa petal extract has a strong anti-oxidant effect. In the present study, we examined if solvent fractions from white rose petal extract (WRPE) had any anti-allergic or anti-atopic effects not previously reported. WRPE and butanol and hexane fractions effectively reduced systemic anaphylactic reactions and anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis in mice, with the greatest inhibition observed for the hexane fraction. In addition, a significant reduction of scratching behavior by mice after histamine injection suggested this fraction's potential anti-allergic effect. At the cell level, the hexane fraction markedly inhibited beta-hexosaminidase release from RBL-2H3 mast cells and suppressed the expressions of mRNA interferon-gamma and interleukin-4 cytokines produced by T helper cells (type 1 and 2). These results strongly support that the hexane fraction may have an effect on atopic dermatitis, as these 2 cell types play central roles in the pathogenesis of atopic dermatitis. In conclusion, these results suggest that either the hexane fraction or one of its components may be beneficial for the treatment of allergic diseases, including atopic dermatitis.


Assuntos
Antialérgicos/farmacologia , Hexanos/farmacologia , Hipersensibilidade Imediata/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Rosa , Anafilaxia/induzido quimicamente , Anafilaxia/tratamento farmacológico , Animais , Células Cultivadas , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Flores/química , Hexanos/isolamento & purificação , Histamina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/metabolismo , beta-N-Acetil-Hexosaminidases/metabolismo , p-Metoxi-N-metilfenetilamina/farmacologia
20.
J Ethnopharmacol ; 122(2): 394-6, 2009 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-19330926

RESUMO

AIM OF THE STUDY: We investigated the effects of Sphaeranthus indicus on mast cell stabilizing activity to provide scientific basis for the clinical use of S. indicus. MATERIALS AND METHODS: The protective effect of different extracts of whole plant of S. indicus against compound 48/80 and sheep serum induced mast cell degranulation was evaluated. RESULTS: Ethanol extract of S. indicus at the doses of 150 mg/kg and 300 mg/kg and ethyl acetate extract at the dose of 100 mg/kg, 150 mg/kg and 300 mg/kg showed slightly better protection of mast cell degranulation (77-86%) than the standard drug ketotifen (75%) in the sheep serum model. These extracts also showed better mast cell stabilizing activity (77-88%) than the standard drug (69%) when peritoneal mast cells are treated with compound 48/80. CONCLUSION: These results suggest that S. indicus has potent mast cell stabilizing effects thereby inhibiting mediator release from mast cells.


Assuntos
Asteraceae , Degranulação Celular/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Hipersensibilidade , Mastócitos/fisiologia , Ratos , Ratos Wistar , Ovinos , p-Metoxi-N-metilfenetilamina/farmacologia
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