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1.
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
2.
Nat Commun ; 11(1): 165, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913280

RESUMO

Targeting of immunoglobulin E (IgE) represents an interesting approach for the treatment of allergic disorders. A high-affinity monoclonal anti-IgE antibody, ligelizumab, has recently been developed to overcome some of the limitations associated with the clinical use of the therapeutic anti-IgE antibody, omalizumab. Here, we determine the molecular binding profile and functional modes-of-action of ligelizumab. We solve the crystal structure of ligelizumab bound to IgE, and report epitope differences between ligelizumab and omalizumab that contribute to their qualitatively distinct IgE-receptor inhibition profiles. While ligelizumab shows superior inhibition of IgE binding to FcεRI, basophil activation, IgE production by B cells and passive systemic anaphylaxis in an in vivo mouse model, ligelizumab is less potent in inhibiting IgE:CD23 interactions than omalizumab. Our data thus provide a structural and mechanistic foundation for understanding the efficient suppression of FcεRI-dependent allergic reactions by ligelizumab in vitro as well as in vivo.


Assuntos
Antialérgicos/administração & dosagem , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Hipersensibilidade/tratamento farmacológico , Omalizumab/administração & dosagem , Animais , Antialérgicos/química , Anticorpos Anti-Idiotípicos/química , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Basófilos/efeitos dos fármacos , Basófilos/imunologia , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/química , Imunoglobulina E/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Omalizumab/química , Receptores de IgE/imunologia
3.
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
4.
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
5.
Org Lett ; 22(2): 580-583, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31880464

RESUMO

Eight unprecedent diterpenoids, botryotins A-H (1-8), were obtained from Botryotinia fuckeliana. They represent three novel carbon skeletons with 6/6/5/5 (1), 6/6/5/6 (2-6), and 6/6/6/5 (7 and 8) tetracyclic scaffolds. Their structures were determined by detailed spectroscopic analysis and chemical derivatization as well as quantum chemical calculation of the ECD and OR data. Botryotin A (1) exhibited a moderate antiallergic effect (IC50 = 0.2 mM). A plausible biosynthetic pathway for 1-8 was proposed.


Assuntos
Antialérgicos/farmacologia , Botrytis/química , Diterpenos/farmacologia , Hipersensibilidade/tratamento farmacológico , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Camundongos , Células RAW 264.7 , Ratos
6.
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
7.
J Agric Food Chem ; 67(43): 11911-11921, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31475818

RESUMO

Red algae sulfated polysaccharides (RASP) were extracted from Porphyra haitanensis and Gracilaria lemaneiformis. RASP were applied to effervescent tablets to develop a type of functional food, termed red algae sulfated polysaccharide effervescent tablets (RASPET), based on the antiallergic activities of RASP. The antiallergic activities and the mechanisms of RASPET were investigated in an ovalbumin (OVA)-induced mouse model of food allergy. The results revealed that RASPET alleviated intestinal villi injury by scanning electron microscopy and anaphylactic symptoms; reduced OVA-specific immunoglobulin E, histamine, and mast cell protease-1 levels in the serum; reduced the level of serum interleukin-4; increased serum interferon-γ level; and decreased B cell and mast cell populations. Remarkably, RASPET increased the levels of serum interleukin-10, transforming growth factor-ß, and upregulated splenic CD4+foxp3+ T cell populations (15.28, 16.82, and 17.58%, respectively) compared to the OVA group (13.17%). In conclusion, RASPET attenuated OVA-induced anaphylaxis via the upregulation of regulatory T cells.


Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos/administração & dosagem , Ovalbumina/efeitos adversos , Polissacarídeos/administração & dosagem , Rodófitas/química , Linfócitos T Reguladores/imunologia , Anafilaxia/etiologia , Anafilaxia/imunologia , Animais , Antialérgicos/química , Modelos Animais de Doenças , Feminino , Histamina/imunologia , Humanos , Imunoglobulina E/imunologia , Interferon gama/imunologia , Interleucina-4/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos/química , Comprimidos/administração & dosagem , Comprimidos/química
8.
J Sci Food Agric ; 99(15): 7008-7015, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31435932

RESUMO

BACKGROUND: Silkworm droppings have long been used in traditional medicine to remedy allergic itching, palsy, blood circulation problems, and arthritis in Asian countries. To investigate the anti-allergic effect of silkworm dropping extract (SDE) and its mechanism, we used a mouse model of food allergy induced by ovalbumin (OVA). RESULTS: SDE ameliorated the symptoms of OVA-induced food allergies, and the levels of T helper 2 (Th2)-related cytokines [such as interleukin (IL)-4, IL-5, IL-10, and IL-13] were found to be significantly decreased in both the spleen and mesenteric lymph nodes by SDE. Furthermore, SDE treatment directly inhibited OVA permeation, IL-4 production, and degranulation of mast cells; in contrast, immunoglobulin E (IgE) production from B cells was not affected. CONCLUSION: These results suggest that SDE has potential anti-allergic activities, and SDE may be useful in the treatment/prevention of allergic disorders such as food allergies, serving as therapeutic agents. © 2019 Society of Chemical Industry.


Assuntos
Antialérgicos/administração & dosagem , Bombyx/química , Fezes/química , Hipersensibilidade Alimentar/tratamento farmacológico , Células Th2/efeitos dos fármacos , Animais , Antialérgicos/química , Feminino , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-5/genética , Interleucina-5/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/efeitos adversos , Células Th2/imunologia
9.
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
10.
J Food Biochem ; 43(1): e12674, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31353487

RESUMO

Mung bean seed is a well-known plant protein consumed in Asian countries but the protein is usually retrieved as a waste product during starch production. This study investigated the anti-allergic property of mung bean protein hydrolysates (MBPH) produced by enzymatic hydrolysis using non-gastrointestinal (non-GI), GI and a combination of non-GI+GI enzymes. The hydrolysates were investigated for any anti-allergic property by detecting the amount of ß-hexosaminidase released in RBL-2H3 cells, and complemented with the MTT assay to show cell viability. It was found that MBPH hydrolyzed by a combination of flavourzyme (non-GI enzyme) and pancreatin (GI enzyme) exhibited the highest anti-allergic activity (135.61%), followed by those produced with alcalase, a non-GI enzyme (121.74%) and 80.32% for pancreatin (GI enzyme). Minimal toxicity (<30%) of all hydrolysates on RBL-2H3 cells line was observed. The results suggest that MBPH can potentially serve as a hypoallergenic food ingredient or supplement. PRACTICAL APPLICATIONS: Mung bean (Vigna radiata L. (Wilczek)) is also known as "green gram" and it is an excellent source of protein. The major mung bean storage proteins are the globulin, albumin and legumin, which are also referred to as legume allergens. Our study showed that mung bean peptides obtained after enzymatic hydrolysis influenced ß-hexosaminidase inhibition without any toxic effect on RBL-2H3 cells. This indicates that mung bean allergenicity can be reduced after enzymatic hydrolysis and the protein hydrolysates could be as a hypoallergic food, ingredient, supplement and/or protein substitute in the formulation of food products.


Assuntos
Antialérgicos/farmacologia , Endopeptidases/metabolismo , Trato Gastrointestinal/enzimologia , Pancreatina/metabolismo , Subtilisinas/metabolismo , Vigna/química , Sequência de Aminoácidos , Animais , Antialérgicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Peptídeos/química , Peptídeos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteólise , Ratos , beta-N-Acetil-Hexosaminidases/antagonistas & inibidores , beta-N-Acetil-Hexosaminidases/metabolismo
11.
Chem Biodivers ; 16(8): e1900237, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31241824

RESUMO

Two new compounds, named 3,4-dimethoxyphenyl α-d-ribofuranoside (1) and 3ß-(ß-d-glucopyranosyloxy)olean-12-ene-23,28,30-trioic acid (2), together with thirteen known compounds, were isolated from the white beans culture of the marine derived endophytic fungus Aspergillus amstelodami. Structure elucidation of the new compounds was carried out by one-, two-dimensional spectroscopy, and high resolution electrospray ionization mass. The antimelanogenic and anti-allergic activity of the isolated compounds were investigated. Compounds 4, 7, 1, 3, 11, 6 and 9 selectively suppressed melanin production in B16 melanoma cells, using arbutin as a positive control. Their IC50 values were 30.8±5.57, 38.5±6.08, 52.6±6.64, 98.0±1.16, 100.4±3.05, 112.0±0.22 and 144.7±2.35 µm, respectively, while that of arbutin was 151.7±1.27 µm. The tested compounds did not show any significant anti-allergic activity in RBL-2H3 cells, as compared to quercetin.


Assuntos
Aspergillus/química , Melaninas/antagonistas & inibidores , Ribose/química , Animais , Antialérgicos/química , Aspergillus/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Hexosaminidases/metabolismo , Espectroscopia de Ressonância Magnética , Melaninas/metabolismo , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Conformação Molecular , Ratos , Ribose/farmacologia , Espectrometria de Massas por Ionização por Electrospray
12.
Int J Pharm ; 567: 118455, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31233846

RESUMO

This study investigates the effects of drug-loaded nanofibers on the solubility of the poorly water-soluble drug, loratadine. Amorphous morphologies of electrospun loratadine nanofibers were prepared using a low-cost 3D-printed electrospinning setup with counter-flow air for the rapid production of nanofibers. Polyvinylpyrrolidone was used as a carrier polymer and ethanol as a solvent in the solution preparation. The prepared nanofibers were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction analysis, Fourier transform infrared spectroscopy, solubility and in vitro dissolution studies with kinetic behavior evaluation. The scanning electron microscope images showed smooth nanofiber surfaces with a mean diameter of 372 nm. Moreover, both differential scanning calorimetry and X-ray diffraction analysis confirmed the amorphous state of the prepared nanofibers. FT-IR results suggested that loratadine lost its original crystal structure by hydrogen bonding interactions. The fabricated nanofibrous drug samples demonstrated a remarkable 26-fold increase in solubility when compared to the pure drug in phosphate buffer at pH 7.4. Furthermore, dissolution studies showed that 66% of the drug from the nanofibrous mat was released in the first 10 min, which is significantly higher than the maximum of 4% drug release of the reference samples within the same time. Thus, Loratadine nanofibers can be considered as an alternative dosage form with improved physicochemical properties.


Assuntos
Antialérgicos/química , Loratadina/química , Nanofibras/química , Povidona/química , Liberação Controlada de Fármacos , Microscopia Eletrônica de Varredura , Nanofibras/ultraestrutura , Impressão Tridimensional , Solubilidade , Tecnologia Farmacêutica
13.
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
14.
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
15.
Drug Deliv Transl Res ; 9(6): 1017-1026, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31049842

RESUMO

The aim of the present study was to fabricate a thermosensitive gel containing chlorpheniramine maleate (CPM)-loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan-based nanoparticles were prepared by a precipitation method followed by the addition of developed NPs within the poloxamer 407- and carbopol 934P-based mucoadhesive thermoreversible gel. Developed formulations were evaluated for particle size, PDI, % entrapment efficiency, and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10 ± 0.414%), and highest drug permeation (90.92 ± 0.531%). The optimized formulation NP3 was then formulated into thermoreversible in situ gel. This intensifies the contact between the nasal mucosa and the drug and increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimized formulation on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the management of allergic rhinitis.


Assuntos
Antialérgicos/administração & dosagem , Quitosana/administração & dosagem , Clorfeniramina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Rinite Alérgica/tratamento farmacológico , Administração Intranasal , Animais , Antialérgicos/química , Quitosana/química , Clorfeniramina/química , Feminino , Géis , Nanopartículas/química , Mucosa Nasal/anatomia & histologia , Mucosa Nasal/química , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Coelhos , Ovinos
16.
Eur J Pharm Sci ; 133: 167-182, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30902654

RESUMO

Thymoquinone is an effective phytochemical compound in the treatment of various diseases. However, its practical administration has been limited due to poor aqueous solubility and bioavailability. In this work, we developed a novel inclusion complex of thymoquinone and hydroxypropyl-ß-cyclodextrin that features improved solubility and bioactivity. The drug solubility was markedly accelerated in the increasing ratio of hydroxypropyl-ß-cyclodextrin to thymoquinone amount. The formation of the thymoquinone/hydroxypropyl-ß-cyclodextrin inclusion complex was evidenced using X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, Fourier transform infrared, scanning electron microscopy and nuclear magnetic resonance. The release behavior of the complex, as well as of their mixtures, was examined in artificial gastric (pH 1.2) and intestinal (pH 6.8) dissolution media. The formulated complex released the drug rapidly at the initial stage, followed by a slow release. Thermodynamic parameters ΔH, ΔS and ΔG were calculated with temperatures ranging from 20 to 45 °C to evaluate the complexation process. The activity of the inclusion complex was evaluated on IgE-mediated allergic response in rat basophilic leukemia (RBL-2H3) cells by monitoring key allergic mediators. The results revealed that compared with free thymoquinone, the inclusion complex more strongly inhibited the release of histamine, tumor necrosis factor-α, and interleukin-4, and was not cytotoxic at the tested thymoquinone concentrations (0.125-4 µg/mL) indicating the inclusion complex possibly had better antiallergic effects. Our finding suggested that the inclusion complex achieved prolonged action and reduced side-effect of thymoquinone.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/administração & dosagem , Antialérgicos/administração & dosagem , Benzoquinonas/administração & dosagem , Sistemas de Liberação de Medicamentos , Animais , Antialérgicos/química , Benzoquinonas/química , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Suco Gástrico/química , Histamina/metabolismo , Interleucina-4/metabolismo , Secreções Intestinais/química , Ratos , Fator de Necrose Tumoral alfa/metabolismo
17.
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
18.
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
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.
Pharmacol Rep ; 71(2): 194-200, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30785056

RESUMO

BACKGROUND: Caffeic amides are derivatives of caffeic acid, which have antioxidant and anti-inflammatory properties, and high in vivo stability. The therapeutic effect of caffeic amides on allergic diseases, and especially on the maturation of bone marrow-derived dendritic cells (BM-DCs), remains unclear. In this study, we investigated the therapeutic potential of caffeic amides on allergic diseases by evaluating the maturation of DCs and evaluated their potential in inducing the differentiation of TH2 cells. METHODS: BM-DCs isolated from BALB/c mice were treated with different caffeic amide derivatives for 48 h and the expression of surface markers was analyzed by flow cytometry. The differentiation of CD4+ T cells was detected by the 5-bromo-2-deoxyuridine (BrdU) incorporation assay and cytokine production was analyzed by ELISA. RESULTS: Our results showed that among the six caffeic amides tested herein, only 36 M significantly inhibited the antigen-induced maturation of DCs associated with the expression of CD80, CD86, and major histocompatibility complex II (VC ovalbumin (OVA)+ thymic stromal lymphopoietin (TSLP) vs. 36 M OVA + TSLP). Additionally, the isolation and co-culture of antigen-specific CD4+ T cells with 36 M-treated BM-DCs suppressed the antigen-specific differentiation of TH2 cells. CONCLUSION: Among the six caffeic amides tested herein, 36 M (N-octyl caffeamide) might possess therapeutic potential for allergic diseases.


Assuntos
Antialérgicos/farmacologia , Ácidos Cafeicos/farmacologia , Células Dendríticas/efeitos dos fármacos , Hipersensibilidade/tratamento farmacológico , Alérgenos/imunologia , Amidas/química , Amidas/farmacologia , Animais , Antialérgicos/química , Células da Medula Óssea/citologia , Ácidos Cafeicos/química , Diferenciação Celular/efeitos dos fármacos , Citocinas/imunologia , Células Dendríticas/citologia , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Hipersensibilidade/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia
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