RESUMO
This study aims to evaluate the analgesic and modulating effect of Curcuma longa and Miconia albicans herbal medicines in knee's osteoarthritis (OA) treatment. This longitudinal study evaluated 24 patients with OA. The patients were divided into three groups: ibuprofen (1200 mg/day), C. longa (1000 mg/day) and M. albicans (1000 mg/day). The medications were applied orally for 30 days. The synovial fluid of the knee joint was collect at the first (day 0) and the last medical (day 30) consultation. The groups treated with herbal medicines presented the same results when compared to Ibuprofen. The comparison of the means of Total WOMAC for M. albicans before and after treatment presented a statistically significant difference (mean day 0 = 57.19; mean day 30 = 31.02) as well as variation of Total WOMAC for C. longa (mean day 0 = 54.79; mean day 30 = 37.08). The WOMAC Total and the VASP were compared, it was found that there was a significant decrease in the means in the C. longa and M. albicans groups, as well as in the Ibuprofen group after treatment. The study demonstrated that the treatment of knee OA with C. longa or M. albicans positively interferes with patients pain and functionality, decreased WOMAC and VASP scores, leading to functional improvement of these patients. This is the first clinical study demonstrating the analgesic and anti-inflammatory effect on knee osteoarthritis from M. albicans comparable to Ibuprofen drug.
Assuntos
Curcuma/química , Melastomataceae/química , Osteoartrite do Joelho/tratamento farmacológico , Extratos Vegetais/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/farmacologia , Artralgia/tratamento farmacológico , Feminino , Humanos , Ibuprofeno/farmacologia , Inflamação/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Resultado do TratamentoRESUMO
Stem cells from human exfoliated deciduous teeth (SHED) have great therapeutic potential and here, by the first time, we evaluated their immunomodulatory effect on experimental model of autoimmune encephalomyelitis (EAE). Specifically, we investigated the effect of SHED administration on clinical signs and cellular patterns in EAE model using Foxp3 GFP + transgenic mice (C57Bl/6-Foxp3GFP). The results showed that SHED infusion ameliorated EAE clinical score with reduced number of infiltrating IFN-γ+CD8+, IL-4+CD8+, IFN-γ+CD4+ and IL-4+CD4+ T cells into the central nervous system (CNS). In addition, we observed that SHED promoted a significant increase in CD4+FOXP3+ T cells population in the spleen of EAE-affected animals. Taken together, our results provide strong evidence that SHED can modulate peripherally the CD4+ T cell responses suggesting that SHED would be explored as part of cellular therapy in autoimmune diseases associated with CNS.
Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Encefalomielite Autoimune Experimental , Transplante de Células-Tronco , Células-Tronco , Dente Decíduo/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/terapia , Xenoenxertos , Humanos , Camundongos , Camundongos Transgênicos , Células-Tronco/imunologia , Células-Tronco/patologia , Dente Decíduo/patologiaRESUMO
Siparuna brasiliensis is a medicinal plant widely used by indigenous communities of the Amazon rainforest to treat inflammatory diseases and related pathologies. Considering its ethnopharmacological application, it constitutes an important source of biologically active molecules in the development of anti-inflammatory drugs. This study describes a dereplication methodology of the bioactive extract from S. brasiliensis leaves and the evaluation of the anti-inflammatory potential in an in vivo inflammatory model with mice of the BALB/c lineage and in vitro using cell lines, as well as determining the production of an inflammatory mediator. From their charge-to-mass ratios (m/z) and elemental composition obtained through Ultrahigh-resolution mass spectrometry analysis by ESI(-)-Orbitrap MS and chromatographic profile by RP-HPLC-PDA, it was possible to annotate polyphenols with anti-inflammatory properties classified as flavonoids and organic acids. The administration of the extract significantly inhibited carrageenan-induced paw edema and showed effects similar to those of drug dexamethasone without affecting cell viability.
Assuntos
Extratos Vegetais , Plantas Medicinais , Camundongos , Animais , Extratos Vegetais/química , Anti-Inflamatórios/química , Carragenina/efeitos adversos , Polifenóis/análise , Folhas de Planta/química , Edema/induzido quimicamente , Edema/tratamento farmacológicoRESUMO
In traditional Brazilian medicine, tubers extracts from Alocasia macrorrhizos are widely used in the treatment of skin pigmentation disorder. However, studies that evaluate its benefits in the treatment of this disorder are non-existent. Thus, this work aims to investigate the bioactivity of A. macrorrhizos extracts in cell culture and murine model of Vitiligo and correlating with its phenolic profile. The metabolic profiling from the bioactive extracts was obtained by LC-DAD-MS, FTIR, NMR, and CE-UV. The murine model of Vitiligo was induced with 5% hydroquinone in C57BL/6 male mice, which were treated or not with 100 mg/kg of roasted tuber aqueous extract. In Vitiligo model assay was observed hair follicle repigmentation and reduction of the epidermal layer thickness at the histopathological level, in the animals treated with aqueous extract of roasted tubers. The present study provides new molecular insight and scientific evidence on the potential utility of the extract of A. macrorrhizos against Vitiligo.
Assuntos
Transtornos da Pigmentação , Vitiligo , Masculino , Animais , Camundongos , Polifenóis/farmacologia , Vitiligo/induzido quimicamente , Vitiligo/tratamento farmacológico , Modelos Animais de Doenças , Espectroscopia de Infravermelho com Transformada de Fourier , Camundongos Endogâmicos C57BLRESUMO
This study describes the extraction and identification by electrophoretic and spectrometric techniques of protease inhibitor from the medicinal plant Alocasia macrorrhizos as well as investigates their immunomodulatory properties and cell viability. The A. macrorrhizos tubers were subjected to protease inhibitor extractions and characterised using SDS-PAGE and MALDI-TOF. The protein extracts were assessed for activities trypsin inhibition stoichiometry, haemagglutinating, cell viability, NO and TNF-α production inhibition. Concerning the protease inhibitors analysis through SDS-PAGE, the results showed two bands with 11 and 24 kDa, and the MS analysis detected the ions more intense of m/z 4276.795 and 8563.361 in the roasted protein extract. The IC50 of trypsin inhibition was 0.119 and 0.302 mg L-1 in the roasted and crude tuber, respectively. The protease inhibitors extract from the roasted tubers showed a reduction in the production of NO and TNF-α at concentrations lower than 100 µg mL-1, without a reduction in cell viability.
RESUMO
The present study highlights the antioxidant and anti-inflammatory activities from Anadenanthera colubrina leaves ethanolic extract (EEAc) and its phytochemical profile. The chemical profile of EEAc was determined and in vitro free radical scavenging potential, cell viability in RAW 264.7 and in vitro and in vivo anti-inflammatory activity were evaluated. The analysis of EEAc showed several phenolic compounds such as tannins and phenolic acids. The high antioxidant potential observed is possibly due to its high phenolic content. The EEAc (500 mg kg-1) showed an in vivo effect at the same level of dexamethasone; in vitro, at 50 µg mL-1, inhibited approximately 80% of nitric oxide production concentration, showed an inhibition of more than 50% of TNF-α production and presented high cell viability. The results show that A. colubrina leaves are an important source of phytochemicals that possesses antioxidant and anti-inflammatory properties.
Assuntos
Colubrina , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Óxido Nítrico , Extratos Vegetais/farmacologia , Folhas de PlantaRESUMO
Our objective is to investigate the phytochemical components, antioxidant capacity and in vitro and in vivo anti-inflammatory action from Cecropia hololeuca bark aqueous extract (AECh). The chemical characterization of AECh was performed through CE-UV, FTIR and NMR Spectroscopy. In vitro assays were performed with the AECh on murine macrophages J774A.1 cells in order to analyse cell viability, NO, TNF-α and IL-1ß productions and the in vivo anti-inflammatory potential in acute carrageenan paw oedema in mice. The AECh showed a decrease in the production of NO, TNF-α and IL-1ß, without altering the cell viability and reduction of the paw thickness in the 2nd, 3rd and 4th hour. The extract presented 72% free radical scavenging, 0.60% flavonoid content and showed the presence of gallic acid, caffeic acid and catechin as major constituents. The C. hololeuca bark extract showed important antioxidant and anti-inflammatory activity, emphasizing the industrial and pharmacological potential of this plant.
Assuntos
Anti-Inflamatórios , Antioxidantes , Cecropia/química , Extratos Vegetais , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Carragenina , Linhagem Celular , Edema/induzido quimicamente , Edema/tratamento farmacológico , Camundongos , Casca de Planta/química , Extratos Vegetais/farmacologiaRESUMO
The isoflavone genistein 1 and some derivatives modulate IL-12, TNF-α and NO production by macrophages and lung cancer cell lines, and improve the clinical signs of experimental autoimmune encephalomyelitis (EAE). Seven genistein derivatives connected at C-6 position of a sugar, such as d-glucose and d-galactose, were synthesized. The ability to modulate macrophage response was evaluated, showing variable inhibition capacity of NO and TNF-α production in J774.A1 and RAW 264.7. Five of the seven compounds were non-cytotoxic; compound 8 was more effective to inhibit NO and TNF-α production, without affecting cell viability.
Assuntos
Galactose/química , Genisteína/química , Genisteína/farmacologia , Glucose/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Óxido Nítrico/biossíntese , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Genisteína/síntese química , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Camundongos , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Mitoxantrone is an anthracene-based anticancer agent whose efficacy in treating autoimmune diseases is believed to be due to cytotoxicity and inhibition of proliferation of cells. Several novel anthraquinone derivatives, analogs of mitoxantrone, were designed and synthesized. Lipophilic and functionalized mitoxantrone analogs were prepared by a simple methodology and the cytotoxicity and the inhibitory effect on nitric oxide release of these compounds were demonstrated in vitro on J774A.1 macrophages. Interestingly compounds 3, 4, 5, 6, 7, and 8 exhibited reduction in NO release (62.4%, 92.6%, 73.4%, 58.4%, 57.8% and 53.4%, respectively) in comparison to NG-n-methyl-arginine treated control, without cytotoxicity. In conclusion, anthraquinone derivatives were prepared in a good yield and showed promissory antiinflammatory properties.
Assuntos
Antraquinonas/toxicidade , Macrófagos/efeitos dos fármacos , Animais , Antraquinonas/química , Anti-Inflamatórios/química , Anti-Inflamatórios/toxicidade , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Estrutura Molecular , Óxido Nítrico/biossínteseRESUMO
Mitoxantrone is an anthracenedione antineoplastic and immunosuppressive agent approved for multiple sclerosis treatment. Novel mono- and disubstituted anthraquinone derivatives, analogues of mitoxantrone, were synthesized through the addition of lipophilic amino alcohols and evaluated for their effect on IL-1ß, TNF-α and nitric oxide production by LPS/IFN-γ-stimulated RAW264.7 cells. The disubstituted 1,4-anthracene-9,10-dione 10 showed significant inhibition of nitric oxide, TNF-α and IL-1ß production at the concentration of 5 µg/mL, with a much lower cytotoxicity than mitoxantrone. The monosubstituted 3, 4, 11, 12 and 13 also displayed a moderate to good inhibitory capacity on IL-1ß production. However, the methylated compounds 11, 12 and 13 failed to inhibit the TNF-α production, and compound 13 was the only one to decrease the production of nitric oxide. None of these derivatives was toxic at the tested concentrations. Compounds 10 and 13 had better inhibitory capacity of the inflammatory mediators analyzed, with reliable viability of the cells.
Assuntos
Antracenos/farmacologia , Interleucina-1beta/metabolismo , Macrófagos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Linhagem Celular , Macrófagos/metabolismo , CamundongosRESUMO
The inflammation process is a coordinated response of the organism related to immune response with release of pro-inflammatory substances, as nitric oxide, TNF-α and IL-1ß. In this work, a series of lipophilic amino alcohols were evaluated on RAW264.7 and primary macrophages for the modulation of nitric oxide and TNF-α. The most potent compounds were submitted to the treatment of BALB/c mice and evaluation of the carrageenan-induced paw edema and TNF-α and IL1-ß release in the paws and anti-OVA delayed type hypersensitivity reaction. RAW264.7 and primary macrophages were incubated in the presence of amino alcohols at different concentrations (1, 0.5, 0.05 and 0.005 µg mL(-1)). All tested compounds were not cytotoxic, however the inhibition of NO and TNF-α were observed only in RAW264.7 cultures. The NO production were reduced in 100% for all compounds, but only the compounds 4a and 4b expressively reduced the TNF-α release (67% and 92% respectively). On the carrageenan-induced paw edema, the compound 4b treatment showed reduction of edema, TNF-α and IL-1ß as efficient as dexamethasone treatment. Meanwhile, the compound 4a treatment showed only slight reduction of paw edema. In the anti-OVA DTH reaction, both compounds showed reduction in the paw edema as effective as dexamethasone. In function of the observed results in vitro and in the acute and anti-OVA inflammation of mice paw edema compound 4b showed promissory anti-inflammatory properties.
Assuntos
Amino Álcoois/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Hipersensibilidade Tardia/tratamento farmacológico , Alérgenos , Amino Álcoois/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Carragenina , Linhagem Celular , Células Cultivadas , Edema/induzido quimicamente , Edema/imunologia , Pé , Hipersensibilidade Tardia/imunologia , Interleucina-1beta/imunologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Ovalbumina , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The present study investigated the effects of the anthraquinone derivative (O,O'-bis-(3'-iodopropyl)-1,4-dihidroxyanthraquinone - DIPDHAQ), mitoxantrone analog, in an experimental autoimmune encephalomyelitis (EAE) model. The results showed that DIPDHAQ treatment improved the clinical signs of the disease (n=10; vehicle: 3.8 ± 0.3; DIPDHAQ: 1.4 ± 0.9). The improvement was associated with a decrease of inflammatory cells, demyelination, IL-17, IFN-γ, IL-12p40, IL-6, TGF-ß, CCL5 and CCL20 levels in the spinal cord. DIPDHAQ presented a low cytotoxicity when in vitro assays were performed. Therefore, the findings suggest a major role for DIPDHAQ in multiple sclerosis, disease characterized as an autoimmune inflammatory disorder against myelin proteins of the brain and spinal cord. The attenuation of inflammation and consequently improvement of clinical signs, involving a decrease of pro-inflammatory cytokines and the low cytotoxicity of DIPDHAQ, suggest that this compound could be used as an alternative treatment for autoimmune diseases in the central nervous system.
Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Macrófagos Peritoneais/efeitos dos fármacos , Mitoxantrona/análogos & derivados , Esclerose Múltipla/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Feminino , Humanos , Imunidade/efeitos dos fármacos , Imunomodulação , Mediadores da Inflamação/metabolismo , Macrófagos Peritoneais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Mitoxantrona/uso terapêutico , Esclerose Múltipla/imunologia , Medula Espinal/metabolismo , Medula Espinal/patologiaRESUMO
Genistein modulates inflammatory responses in part by reducing the production of the pro-inflammatory cytokines IL-12, TNF-α, and nitric oxide, by activated macrophages in response to lipopolysaccharide stimulus. Previous studies have shown that synthetic lipophilic genistein glycosides were significantly more active than hydrophilic glycosides. The aims of this study were to synthesize and to evaluate the effect of novel lipophilic genistein derivatives on IL-12, TNF-α, and nitric oxide production by J774A.1 cells. The results show that the modification of genistein enables the generation of non-cytotoxic compounds with increased IL-12 inhibition. However, these derivatives failed to inhibit TNF-α. The nitric oxide production was notably inhibited by the monoester (2, 3) and monoether (6, 7) compounds in a dose-dependent manner.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Genisteína/análogos & derivados , Genisteína/farmacologia , Interleucina-12/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Linhagem Celular , Genisteína/síntese química , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico/metabolismoRESUMO
Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis (MS), a human inflammatory demyelinating disease of the central nervous system. Genistein, an isoflavonoid phytoestrogenic compound found in soy, is known to reverse clinical signs of EAE. Although genistein has some potential in clinical application, it has some disadvantages related to its chemical structure, such as rapid in vivo metabolism and a fast decline in serum after oral administration. The present work investigates the treatment of EAE by using 7-O-tetradecanoyl-genistein (TDG), a more lipophilic analog of genistein obtained by esterification. The clinical course of EAE was investigated in C57Bl/6 mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG)(35-55) in complete Freund's adjuvant supplemented with Mycobacterium tuberculosis H37RA. After 14 days of MOG immunization, mice were treated with TDG for seven days. Numbers of IL-17-producing cells and Foxp3 by CD4(+) T cells and CTLA-4 expression by CD3(+) T cells from brain were determined by flow cytometry. Levels of IL-6, IFN-γ and IL-10 were evaluated by ELISA. Brain sections were stained by hematoxylin and eosin method. The data obtained indicate that TDG treatment ameliorates the clinical signs of EAE, which correlates with a decrease of IL-17-producing cells and an increase in Foxp3(+)CD4(+) cells in the brain. TDG is also shown to enhance IL-10 production and CTLA-4 expression and to reduce IFN-γ and IL-6. Altogether, these findings suggest an immunomodulatory therapeutic role for TDG in EAE and multiple sclerosis.
Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/imunologia , Genisteína/análogos & derivados , Genisteína/farmacologia , Fatores Imunológicos/imunologia , Fatores Imunológicos/farmacologia , Adjuvantes Imunológicos/farmacologia , Animais , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Complexo CD3/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Antígeno CTLA-4/metabolismo , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Adjuvante de Freund/imunologia , Genisteína/imunologia , Interferon gama/imunologia , Interleucinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Mycobacterium tuberculosis/imunologia , Proteínas da Mielina/imunologia , Glicoproteína Mielina-OligodendrócitoRESUMO
This work reports the preparation of several amino alcohols condensed with d-arabinose, d-glucose, and d-galactose derivatives. These compounds were evaluated in vitro for their cytotoxicity and ability to decrease nitric oxide production in J774A.1 cells. Arabinofuranoside derivatives 5a, 5b and 5c showed a significant inhibition of nitric oxide production (>80% at 5 µg/mL), while the galactopyranoside derivative 8d showed a notable nitric oxide inhibitory activity (126% at 0.5 µg/mL).