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1.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3441-3447, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602907

RESUMO

To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 µg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Tripterygium/química , Inibidores da Angiogênese/farmacologia , Angiotensina I/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Membrana Sinovial/efeitos dos fármacos , Comprimidos , Fator A de Crescimento do Endotélio Vascular
2.
Phytomedicine ; 63: 153036, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401534

RESUMO

BACKGROUND: Genkwanin is a flavone isolated from the traditional Chinese herb Daphne genkwa. Our previous work proved that four flavonoids (including genkwanin) isolated from D. genkwa (FFD) significantly improved the symptoms of arthritis in rat models. Recent studies have revealed that genkwanin exhibited anti-inflammatory and immunomodulatory activities, both of which were closely related to the pathology of rheumatoid arthritis (RA). Therefore, studying the anti-RA effects and mechanisms of genkwanin may give us insight into FFD's therapeutic effects on RA. PURPOSE: This study aimed to investigate the anti-rheumatoid arthritis activity of genkwanin on adjuvant-induced arthritis (AIA) model in rats and explore the underlying mechanisms. METHODS: The anti-rheumatoid arthritis activity of genkwanin was evaluated on AIA rat model by determining the paw swelling degrees and arthritis index scores, along with histopathological analysis of joint tissues. The serum cytokine levels were measured by ELISA method, and serum NO levels were measured by Griess method. The expression and phosphorylation levels of proteins in JAK/STAT and NF-κB signaling pathways were determined by western blot analysis and immunohistochemistry analysis. RESULTS: Genkwanin significantly decreased the paw swelling and arthritis index in AIA rats and also decreased the inflammation and bone destruction in joint tissues. The serum TNF-α, IL-6, and NO concentrations were markedly reduced while the IL-10 concentration was markedly increased with the treatment of genkwanin. Genkwanin inhibited the activation of JAK/STAT and NF-κB signaling pathways in synovial tissues of AIA rats. CONCLUSION: Genkwanin exerted anti-rheumatoid arthritis effects on AIA rats through inhibiting the activation of JAK/STAT and NF-κB signaling pathways. The results obtained in this work lead us to suggest that Genkwanin could play a crucial role on the previously demonstrated anti-rheumatoid arthritis activity of flavonoid extract of D. genkwa (namely FFD).


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Flavonas/farmacologia , NF-kappa B/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inibidores de Janus Quinases/farmacologia , Masculino , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Fatores de Transcrição STAT/antagonistas & inibidores , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia
3.
Phytother Res ; 33(11): 2971-2978, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31407455

RESUMO

Moutan Cortex has been widely used to treat various types of arthritis in traditional Chinese medicine. Paeonol is isolated as an active ingredient from Moutan Cortex. However, the effect and potential mechanism of paeonol on gouty arthritis have not been evaluated. In this study, rats were treated intragastrically with paeonol for consecutive 7 days. On Day 5, rats were intra-articularly injected with monosodium urate (MSU) crystals in the ankle joints to induce MSU-induced arthritis (MIA). Paw volume was detected at various time points. Gait score was measured at 24 hr after MSU crystal injection. Ankle joints were collected for evaluation of histological score and expression of proinflammatory cytokines using hematoxylin and eosin staining and immunohistochemistry staining, respectively. Nuclear level of nuclear factor (NF)-κBp65 in synovial tissues was analyzed by western blot assay. NF-κB DNA-binding activity was measured by enzyme linked immunosorbent assay. Paeonol markedly lowered the paw volume, gait score, and histological score in MIA rats. Mechanistically, paeonol markedly reduced the expression of TNF-α, IL-1ß, and IL-6 in synovial tissues of MIA rats. In addition, the elevated level of p65 in nucleus and NF-κB DNA-binding activity in synovial tissues of MIA rats were reduced significantly by paeonol treatment. These findings suggest that paeonol exerts anti-inflammatory effect in MIA rats through inhibiting expression of proinflammatory cytokines and NF-κB activation.


Assuntos
Acetofenonas/uso terapêutico , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/prevenção & controle , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Ácido Úrico , Animais , Artrite Gotosa/metabolismo , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Marcha/efeitos dos fármacos , Análise da Marcha , Masculino , NF-kappa B/metabolismo , Paeonia/química , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos
4.
BioDrugs ; 33(4): 391-399, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172372

RESUMO

Psoriasis is a chronic inflammatory skin disease with significant psychological and physical impact. Over the last few decades, several highly effective target therapies have been developed, leading to a major paradigm shift in the way psoriatic disease is managed. Despite this, a proportion of patients still do not respond or lose response over time. Bispecific antibodies target two different cytokines simultaneously, potentially offering a better disease control. Interleukin (IL)-17A and IL-17F share structural homology and have similar biologic function. IL-17A is classically considered to be the most biologically active, but recent studies have shown that IL-17F is also increased in psoriatic skin and synovial cell in psoriatic arthritis, supporting the rationale for targeting both IL-17A and IL-17F in psoriatic disease. Bimekizumab is the first-in-class monoclonal antibody designed to simultaneously target IL-17A and IL-17F. Bimekizumab is currently in clinical development for psoriasis, psoriatic arthritis, and ankylosing spondylitis, with promising results. In early clinical trials, bimekizumab demonstrated a rapid onset of action, good safety profile, and high tolerability by treated study participants. Long-term results and head-to-head trials comparing bimekizumab with other agents will be crucial to define the role of bimekizumab in the treatment of psoriatic disease.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Psoríase/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Ensaios Clínicos como Assunto , Humanos , Interleucina-17/antagonistas & inibidores , Interleucina-17/imunologia , Psoríase/imunologia , Pele/efeitos dos fármacos , Pele/imunologia , Espondilite Anquilosante/imunologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Resultado do Tratamento
5.
Int Immunopharmacol ; 73: 539-551, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177080

RESUMO

OBJECTIVE: We aimed to investigate the immunologic mechanisms by which arsenic trioxide (As2O3) may inhibit T helper 17 (Th17) cell differentiation while promoting regulatory T (Treg) cell generation by modulating signal transducer and activator of transcription 3 (STAT3) in treatment-naïve rheumatoid arthritis (RA) patients. METHODS: Naïve CD4+T cells isolated by fluorescence-activated cell sorting from treatment-naïve RA patients and healthy controls were used to investigate the effect of As2O3 on the process of polarization and the related cytokines. STAT3 transfection experiments were conducted with small interfering RNA (siRNA) and lentivirus STAT3 to verify the mechanism of As2O3 on Th17-Treg balance in vitro. A collagen-induced arthritis (CIA) model was used to detect the clinical scores, histopathological change, bone destruction, Th17-Treg proportion and joint tissue immunohistochemistry. RESULTS: We found that As2O3 prevented activated naïve CD4+T-cells from differentiating into Th17 cells and reduced cytokine production by activated Th17 cells by downregulating their signature transcription factors, STAT3 and orphan nuclear receptors. Notably, As2O3 reduced Th17 cells frequency while increasing Treg cells frequency under specific polarizing conditions in treatment-naïve RA patients by transfecting siRNA STAT3 and lentivirus STAT3. Furthermore, we noticed that applying As2O3 in the CIA model attenuated the infiltration of joint inflammation and bone destruction, and significantly improved the imbalanced Treg-Th17 ratio. CONCLUSIONS: These data indicate that As2O3 may be a potential immune modulator for treatment-naïve RA patients that helps to balance of Treg and Th17 cells through modulating STAT3.


Assuntos
Trióxido de Arsênio/farmacologia , Artrite Reumatoide/imunologia , Fatores Imunológicos/farmacologia , Fator de Transcrição STAT3/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Adulto , Animais , Trióxido de Arsênio/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Artrite Experimental/patologia , Citocinas/imunologia , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Baço/efeitos dos fármacos , Baço/imunologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia
6.
BMC Musculoskelet Disord ; 20(1): 286, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31200688

RESUMO

BACKGROUND: McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop destructive arthritis and enthesitis in the ankle. There is no published data that drug treatment has been trialed on these mice. This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16-1, for the treatment of arthritis and enthesitis in McH-lpr/lpr-RA1 mice. METHODS: Male McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16-1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines. RESULTS: Tissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the control group at 14 and 17 weeks of age. The kappa coefficient was 0.77. However, progression of entheseal ossification persisted in the MR16-1 treated group. In vivo imaging using indocyanine green liposomes showed significant decreases in signal intensities of treated groups at week 14, but no significant differences were observed at week 18. Blood serum amyloid A levels in treated groups were significantly lower at 17 weeks of age. The gene expression levels of Tnf and Il17 were also significantly lower in MR16-1 treated groups. CONCLUSIONS: Administration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for destructive arthritis and enthesitis. IL-6 signal blockade could contribute to the treatment of destructive arthritis, and further studies should be carried out to confirm its potential in the prevention of enthesopathy developed to ossification.


Assuntos
Anticorpos/administração & dosagem , Artrite/tratamento farmacológico , Entesopatia/tratamento farmacológico , Receptores de Interleucina-6/antagonistas & inibidores , Animais , Artrite/imunologia , Artrite/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Entesopatia/imunologia , Entesopatia/patologia , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos , Distribuição Aleatória , Receptores de Interleucina-6/imunologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia
7.
Int Immunopharmacol ; 73: 362-369, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132731

RESUMO

Apigenin (API) is a plant flavone that is known to exert a protective effect in rheumatoid arthritis (RA), which is a chronic autoimmune disease. However, the molecular mechanism for API's protective effect against RA is still unclear. Here, a collagen-induced arthritis (CIA) mouse model was used to assess the protective effect of API on RA. Histomorphological studies, immunohistochemistry, RT-PCR, and western blot were conducted to elucidate the roles of synovial hyperplasia, angiogenesis, and osteoclastogenesis in the protective effect of API on RA. Fibroblast-like synoviocytes (FLSs) were isolated to measure the effect of API on FLS proliferation and apoptosis. API exhibited a significant protective effect in CIA mice in a dose- and time-dependent manner. An increase in apoptosis and decrease in proliferation were observed after the API treatment in FLSs, suggesting that API might inhibit synovial hyperplasia. Moreover, CIA angiogenesis was repressed by API via down-regulation of VEGF and VEGFR. Furthermore, API regulated the osteoclastogenesis-associated RANKL/RANK/OPG system in CIA mice. Therefore, API inhibits CIA by repressing synovial hyperplasia, angiogenesis, and osteoclastogenesis. This suggested that API might be a putative low toxicity candidate drug for RA treatment.


Assuntos
Antirreumáticos/uso terapêutico , Apigenina/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Animais , Antirreumáticos/farmacologia , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Artrite Experimental/genética , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Hiperplasia/tratamento farmacológico , Hiperplasia/genética , Hiperplasia/metabolismo , Hiperplasia/patologia , Masculino , Camundongos Endogâmicos DBA , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Sinoviócitos/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Acta Orthop Traumatol Turc ; 53(4): 292-296, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30982756

RESUMO

OBJECTIVE: The aim of this animal study was to investigate the short and long-term local histomorphologic effects and the utility of intra-articular application of ibuprofen. METHODS: Forty-six Wistar Albino rats were used in the study. The rats were randomized into 5 groups of 8 and a sham group of 6. The 40 rats in the study groups were anaesthetised with 60 mg/kg of ketamine, then 0.25 ml ibuprofen (25 mg) was injected to the right knee joint of each rat (ibuprofen group) and 0.25 ml 0.9% saline to the left knee joint as the control group. To the 6 rats in the sham group, only puncture was applied to both knee joints. The rats in each of the 5 study groups were sacrificed on days 1, 2, 7, 14 and 21 respectively. The histomorphologic changes were graded on a 6-point scale regarding inflammation of the synovia, cartilage tissue, and subchondral bone. Inflammation scores were compared using the Mann Whitney U-test and comparisons of the sacrifice day and drug used were evaluated with the Kruskal Wallis test. The p values below 0.05 were considered as significant. RESULTS: Statistically significant difference was found between the ibuprofen injected knees (10/40) and the saline injected (0/40) and sham knees (0/12) in respect of hematoma positivity (p = 0.002). Significantly higher inflammation scores were found in ibuprofen injected knees on the 1st, 2nd, 7th and 14th days compared to controls and sham (p < 0.05). Inflammation scores were similar in ibuprofen injected knees with and without hematoma (p > 0.05). Inflammation of the ibuprofen injected group was most severe on day one and the severity of inflammation reduced gradually throughout the 3 weeks. CONCLUSION: Our results show that intra-articular injection of ibuprofen can cause intra-articular hematoma. It also leads to transient inflammation of the synovia that is more severe in the early period, which gradually recovers.


Assuntos
Ibuprofeno/administração & dosagem , Inflamação , Injeções Intra-Articulares/métodos , Osteoartrite do Joelho/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Cartilagem Articular/efeitos dos fármacos , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/patologia , Articulação do Joelho/patologia , Masculino , Ratos , Ratos Wistar , Membrana Sinovial/efeitos dos fármacos , Resultado do Tratamento
9.
Drugs ; 79(4): 455-462, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30847805

RESUMO

Triamcinolone acetonide extended-release (ER) 32 mg (Zilretta®) is approved in the USA for the management of osteoarthritis (OA) pain of the knee and is administered as a single, 5 mL intra-articular (IA) injection. Although the therapeutic effects from IA corticosteroids are typically short-lived, triamcinolone acetonide ER is formulated in poly (lactic-co-glycolic acid) (PLGA) microspheres that slowly release triamcinolone acetonide in the synovium, enabling their prolonged presence in the joint. This reduces systemic exposure and lessens corticosteroid-related systemic adverse reactions, such as blood glucose elevations. In a 24-week, randomized, phase III clinical trial, triamcinolone acetonide ER 32 mg significantly improved mean average daily pain intensity in patients with knee OA relative to placebo, and pain, stiffness and physical function (according to WOMAC criteria) relative to placebo and triamcinolone acetonide crystalline suspension (CS). Triamcinolone acetonide ER was generally well tolerated, with a tolerability profile similar to that of triamcinolone acetonide CS and placebo. Findings from a single-arm phase IIIb study indicated that a repeat administration of triamcinolone acetonide ER may be similarly efficacious to an initial injection without having deleterious effects on cartilage or other aspects of joint structure. Thus, triamcinolone acetonide ER expands the treatment options available for the management of OA pain of the knee.


Assuntos
Preparações de Ação Retardada/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Preparações de Ação Retardada/efeitos adversos , Aprovação de Drogas , Sistemas de Liberação de Medicamentos , Humanos , Injeções Intra-Articulares , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ensaios Clínicos Controlados Aleatórios como Assunto , Membrana Sinovial/efeitos dos fármacos , Triancinolona Acetonida/efeitos adversos , Estados Unidos , United States Food and Drug Administration
10.
J Nutr Sci Vitaminol (Tokyo) ; 65(1): 8-18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814416

RESUMO

The present study was conducted to assess the effect of all-trans retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were excised from the knees of healthy adult Wistar female rats under sterile conditions. We first investigated the synoviums incubated in a control medium or in a medium containing 10 µg/mL LPS, each for 24, 48, and 72 h (LPS-experiment). The changes in inflammatory response from the synoviums were observed at different culture times. Then, we assessed the synoviums exposed to different ATRA concentrations for 24 h (ATRA-experiment). The controls (blank, model group, and solvent groups) were set up. The effects of ATRA on synovitis were evaluated by measuring the production of cytokines, and nitric oxide (NO) and the expression of cartilage damage related proteases. In the LPS-experiment, LPS contributed to the release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) in synovial explants. Importantly, LPS did not cause a significant pathological damage. The inflammatory response observed in this model was significant for 24 h, suggesting that LPS-induced synovial explants were successfully established. In the ATRA-experiment, ATRA suppressed the expression of IL-6, TNF-α, NO, a disintegrin and metalloprotease with thrombospondin motifs-4 (ADAMTS-4), MMP-3, and MMP-9. Taken together, ATRA exhibited inhibitory effects on LPS-induced synovial immune inflammatory response stimulated by the regulation of inflammatory mediators and cartilage damage related proteases in synovial explants, demonstrating a potential protective effect on synovitis and joint destruction in the patients with RA.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Reumatoide/tratamento farmacológico , Articulação do Joelho/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Tretinoína/farmacologia , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Lipopolissacarídeos , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico , Sinovite/metabolismo
11.
Drug Deliv ; 26(1): 226-236, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30843733

RESUMO

Inflammation of the synovium and joint capsule is a main driver of pain in an osteoarthritic (OA) joint. Triamcinolone acetonide (TAA) is a classical corticosteroid that reduces synovitis and alleviates pain, albeit transiently. Biomaterial-based local TAA release may prolong the suppression of pain without the need for multiple injections. Polylactic-co-glycolic acid (PLGA) formulations of TAA prolong OA pain relief to a limited extent. A novel polyesteramide (PEA) microsphere platform allows for extended release in the OA joint for over 3 months. To evaluate their effect on pain and inflammation, TAA-loaded microspheres were intra-articularly delivered to the knee joint in a rat model of acute arthritis induced by intra-articular injection of streptococcal cell wall peptidoglycan-polysaccharide (PGPS) and subsequent flare-ups by intravenous PGPS injections. PEA-loaded microspheres were benchmarked with TAA-loaded PLGA microspheres and bolus TAA injection. TAA treatments were injected intra-articularly before the first induced flare-up. TAA-loaded PEA and PLGA microspheres reduced joint swelling and signs of pain-like behavior over the entire study period, as assessed by weight bearing and referred mechanical hypersensitivity, whereas bolus suspension was effective for a shorter time period. TAA-loaded PEA microspheres reduced lameness to a greater extent than TAA-loaded PLGA microspheres. In conclusion, a single intra-articular injection of TAA-loaded PEA microspheres reduced joint swelling and induced longer pain relief compared to bolus injection. Hence relief of inflammation and pain by PEA-based delivery of TAA may prove to be effective and durable.


Assuntos
Materiais Biocompatíveis/farmacologia , Inflamação/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Triancinolona Acetonida/farmacologia , Resinas Acrílicas/química , Animais , Materiais Biocompatíveis/química , Modelos Animais de Doenças , Feminino , Injeções Intra-Articulares/métodos , Articulação do Joelho/efeitos dos fármacos , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos , Ratos Sprague-Dawley , Membrana Sinovial/efeitos dos fármacos , Triancinolona Acetonida/química
12.
Phytomedicine ; 58: 152825, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30831463

RESUMO

BACKGROUND: The seeds of Vitex negundo, with rich lignans metabolites, have been widely used as a traditional Chinese medicine and Ayurvedic herbal medicine for the treatment of rheumatism and joint inflammation. The total lignans of Vitex negundo seeds (TOV) were suggested to play an important role in the treatment of arthritis. PURPOSE: The aim of the study was designed to investigate the anti-arthritic effects of TOV on collagen-induced arthritis (CIA) in rats as well as its possible mechanisms. METHODS: TOV was prepared by combined macroporous resin and polyamide column chromatography, and constituents of TOV were analyzed by HPLC. CIA model in rats was established by immunization with chicken type II collagen and then the rats were intragastrically administrated with TOV for 30 days. Rat arthritis was evaluated by measurements of hind paw edema, arthritis index score, weight growth and indices of thymus and spleen, and by histological examination. Levels of serum MMP-2, MMP-3, MMP-9, IL-1ß, IL-6, IL-8, IL-10, IL-17A and TNF-α were also examined. In addition, the expression of COX-2, iNOS and IκB, p-IκB in synovial tissues was evaluated by western blotting. The analgesic and anti-inflammatory effects of TOV were also evaluated in acetic acid-induced writhing and xylene-induced ear edema in mice, respectively. In addition, acute toxicity test was employed to preliminarily assess the safety of TOV. RESULTS: TOV significantly inhibited the paw edema and decreased the arthritis index, with no influence on the body weight and the indices of thymus and spleen of CIA rats. Meanwhile, TOV dose-dependently reduced the infiltration of inflammatory cells, synovial hyperplasia and attenuated cartilage damage. Additionally, the serum levels of IL-1ß, IL-6, IL-8, IL-17A, TNF-α, MMP-3 and MMP-9 were markedly decreased, while the level of serum IL-10 was increased in TOV-treated rats. The significant reduction of the expression of COX-2, iNOS and p-IκB and the notable increase of IκB in synovial tissues were also observed in TOV-treated animals. TOV also significantly inhibited acetic acid-induced writhing and decreased xylene-induced ear edema in mice. Finally, the maximal tolerable dose (MTD) of TOV was determined to be 16.0 g/kg. CONCLUSION: These results suggest that TOV has significant anti-arthritic effects on collagen-induced arthritis in rats, which may be attributed to the inhibition of the levels of IL-1ß, IL-6, IL-8, IL-17A, TNF-α, MMP-3 and MMP-9, and the increase of IL-10 in serum as well as down-regulation of the protein expression of COX-2 and iNOS in synovial tissues via suppressing the phosphorylation and degradation of IκB. Due to its high efficacy and safety, TOV can be regarded as a promising drug candidate for rheumatoid arthritis treatment.


Assuntos
Artrite Experimental/tratamento farmacológico , Edema/tratamento farmacológico , Lignanas/farmacologia , Medicina Tradicional Chinesa , Vitex/química , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/patologia , Galinhas , Colágeno Tipo II/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Citocinas/sangue , Edema/patologia , Feminino , Masculino , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Sementes/química , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia
13.
BMC Complement Altern Med ; 19(1): 47, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755211

RESUMO

BACKGROUND: Libidibia ferrea (L. ferrea) has been used in folk medicine to treat several conditions and to prevent cancer. This study performed a chromatographic analysis of the crude aqueous extract of Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz (LfAE) leaves and evaluated its in vivo antioxidant and anti-inflammatory potential. METHODS: Polyphenols present in LfAE were characterized by high performance liquid chromatography (HPLC). Anti-inflammatory activity was studied in an experimental model of zymosan-induced intra-articular inflammation, conducted in Wistar rats treated with LfAE at the doses of 100, 200 and 300 mg/kg by gavage. Synovial fluid was collected for global leukocyte count, for spectrocopical UV/VIS analysis of myeloperoxidase (MPO) activity, total glutathione and malondialdehyde (MDA), and for quantification of inflammatory cytokines IL1-ß and TNF-α by enzyme-linked immunosorbent assay. Synovial membrane was collected for histological analysis. The level of statistical significance was p < 0.05. RESULTS: HPLC detected concentrations of 1.56 (0.77) %m/m for ellagic acid and 1.20 (1.38) %m/m for gallic acid in LfAE leaves. Treatment with LfAE at all doses significantly decreased the leukocyte influx into the synovial fluid (p < 0.001) and myeloperoxidase activity (p < 0.001), an important marker of neutrophils. LfAE at doses of 100 (p < 0.05), 200 and 300 mg/kg (p < 0.001) also reduced the levels of MDA. LfAE at doses of 200 and 300 mg/kg significantly decreased the levels of IL-1ß (p < 0.05) and TNF-α (p < 0.001). All doses of LfAE resulted in increased levels of total glutathione (p < 0.001). Histopathological findings confirmed a reduction of the inflammatory infiltrate in the rats treated with LfAE at a dose of 200 mg/kg (p < 0.05). CONCLUSION: LfAE has an important anti-oxidant and anti-inflammatory effect on intra-articular inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Caesalpinia/química , Inflamação/metabolismo , Extratos Vegetais/farmacologia , Animais , Antioxidantes/metabolismo , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Citocinas/metabolismo , Inflamação/induzido quimicamente , Masculino , Folhas de Planta/química , Ratos , Ratos Wistar , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Zimosan
14.
BMC Musculoskelet Disord ; 20(1): 76, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764805

RESUMO

BACKGROUND: Data from a recent clinical trial of vitamin D therapy in knee OA suggests that, compared to placebo, vitamin D therapy may be associated with a reduction in effusion-synovitis. Our aim was, using contrast-enhanced (CE) magnetic resonance imaging (MRI), to examine the effect of vitamin D therapy on synovial tissue volume (STV) and also subchondral bone marrow lesion (BML) volume in men and women with symptomatic knee OA. METHODS: Data was acquired from participants who took part in a randomised placebo-controlled trial (UK VIDEO) investigating the effect of vitamin D therapy (800 IU cholecalciferol daily) on radiographic joint space narrowing. A subsample had serial CE MRI scans acquired during the trial. Subjects with serial images were assessed (N = 50) for STV and subchondral BML volume. The difference in the mean change from baseline in these structural outcomes between intervention and placebo groups was assessed using random-effects modelling. RESULTS: The mean age of the 50 subjects (24 active group, 26 placebo group) who contributed data to the analysis was 63.3 years (SD 6.5) and 74% were female. There was no significant difference at 2 years follow-up between the vitamin D and placebo groups in the mean change from baseline for STV (93.9 mm3, 95% CI -1605.0 to 1792.7) and subchondral BML volume (- 313.5 mm3, 95% CI -4244.7 to 3617.7). CONCLUSIONS: Vitamin D supplementation does not appear to have an effect on synovitis or BML volume in patients with symptomatic knee OA. TRIAL REGISTRATION: VIDEO was registered with EudraCT: ref. 2004-000169-37. The protocol for the trial can be accessed at https://www.ctu.mrc.ac.uk/studies/all-studies/v/video/.


Assuntos
Medula Óssea/efeitos dos fármacos , Colecalciferol/administração & dosagem , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Membrana Sinovial/efeitos dos fármacos , Sinovite/tratamento farmacológico , Vitaminas/administração & dosagem , Idoso , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Colecalciferol/efeitos adversos , Método Duplo-Cego , Inglaterra , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologia , Sinovite/diagnóstico por imagem , Sinovite/patologia , Fatores de Tempo , Resultado do Tratamento , Vitaminas/efeitos adversos
15.
Phytomedicine ; 57: 271-281, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30802713

RESUMO

BACKGROUND: The stems of Tinospora sinensis (Lour.) Merr commonly named "Kuan-Jin-Teng" in Chinese, have been used to treat rheumatoid arthritis as a Tibetan medicine. PURPOSE: The effects of the EtOAc fraction of ethanolic extract from the stems of T. sinensis (KJT) on the pro-inflammatory cytokines and MAPK pathway were studied in collagen-induced arthritis (CIA) model. STUDY DESIGN: Anti-arthritic activity of KJT was investigated in CIA model. METHODS: The chemical constituents of KJT were analyzed by LC-MS and HPLC. The CIA model was established with injecting the bovine CII emulsified in Freund's adjuvant in Wistar rats. Several doses of KJT (50.0, 100.0 and 200.0 mg/kg) were administrated via oral gavage to CIA rats daily for 4 weeks. The anti-arthritic activity of KJT was investigated by clinical arthritis scoring, paw swelling inspection and hyperalgesia measurement, as well as radiological and histological analysis in CIA rats. The impacts of KJT on the activation of MAPK pathway, production of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-17) in ankle joints, serum, and spleen in CIA rats were examined by western blot, immunohistochemical staining, ELISA, and quantitative real-time PCR respectively. Lastly, the effects of KJT on production of the nitric oxide (NO) and pro-inflammatory cytokines as well as the regulation of the phosphorylation of p38 and Erk were detected in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells. RESULTS: KJT significantly alleviated the paw swelling, hyperalgesia and arthritic severity, and reduced the synovial tissue proliferation and inflammatory cell infiltration in the CIA rats. Moreover, KJT suppressed the production of TNF-α, IL-1ß, and IL-17 in ankle joints, serum, and spleen and reversed the up-regulation of the phosphorylation of p38 and Erk in CIA rats. KJT was also demonstrated to inhibit the production of NO and pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), and phosphorylation of p38 and Erk in LPS-stimulated RAW264.7 cells. CONCLUSION: These results suggest the mechanisms of KJT performing its anti-arthritis effect may be attributed to inhibiting the production of pro-inflammatory cytokines and down-regulating the MAPK signaling pathway.


Assuntos
Artrite Experimental/tratamento farmacológico , Citocinas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Colágeno/toxicidade , Regulação para Baixo/efeitos dos fármacos , Edema/tratamento farmacológico , Edema/patologia , Adjuvante de Freund/efeitos adversos , Masculino , Medicina Tradicional Tibetana , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Ratos Wistar , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Tinospora/química
16.
J Agric Food Chem ; 67(10): 2856-2864, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30785275

RESUMO

Among the various treatments, induction of synoviocyte apoptosis by natural products during a rheumatoid arthritis (RA) pathological condition can be considered to have vast potential. However, it is unclear that liquiritin, a kind of natural flavonoid extracted from the roots of Glycyrrhiza uralensis, induced the apoptosis of the synovial membrane and its molecular mechanism. In this study, interleukin-1ß (IL-1ß)-RA-FLS cells were incubated with different concentrations of liquiritin. An MTT assay, Hoechst 33342 staining, JC-1 staining, and Western blot were used to check the viability, cell apoptosis, mitochondrial membrane potential changes, and the expression of related proteins, respectively. In vivo, a TUNEL assay and HE staining of tissue were used for histopathological evaluation. Our results showed that liquiritin significantly inhibited the proliferation of IL-1ß-induced-RA-FLS, promoted nuclear DNA fragmentation, and changed the mitochondrial membrane potential to accelerate cell apoptosis. Liquiritin downregulated the ratio of Bcl-2/Bax and inhibited the VEGF expression and phosphorylation of JNK and P38. Moreover, liquiritin improved the clinical score of rheumatism, inflammatory infiltration, and angiogenesis and induced apoptosis of the synovial tissue in vivo. Hence, liquiritin ameliorates RA by reducing inflammation, blocking MAPK signaling, and restraining angiogenesis.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , Flavanonas/administração & dosagem , Glucosídeos/administração & dosagem , Glycyrrhiza uralensis/química , Neovascularização Patológica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Neovascularização Patológica/fisiopatologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
17.
Eur J Pharm Biopharm ; 136: 84-92, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30659893

RESUMO

In the present work curcumin loaded hyalurosomes were proposed as innovative systems for the treatment of rheumatoid arthritis. Vesicles were prepared using a one-step and environmentally friendly method. Aiming at finding the most suitable formulation in terms of size, surface charge and stability on storage, an extensive pre-formulation study was performed using different type and amount of phospholipids. Curcumin loaded vesicles prepared with 180 mg/ml of Phospholipon 90G (P90G) and immobilized with sodium hyaluronate (2 mg/ml) were selected because of their small size (189 nm), homogeneous dispersion (PI 0.24), negative charge (-35 mV), suitable ability to incorporate high amount of curcumin (E% ∼88%) and great stability on storage. The in vitro study using fibroblast-like synovial cells cultured in synovial fluid, demonstrated the ability of these vesicles to downregulate the production of anti-apoptotic proteins IAP1 and IAP2 and stimulate the production of IL-10, while the production of IL-6 and IL-15 and reactive oxygen species was reduced, confirming their suitability in counteracting pathogenesis of rheumatoid arthritis.


Assuntos
Artrite Reumatoide/metabolismo , Curcumina/administração & dosagem , Ácido Hialurônico/administração & dosagem , Mediadores da Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Líquido Sinovial/metabolismo , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Curcumina/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Ácido Hialurônico/química , Mediadores da Inflamação/antagonistas & inibidores , Estresse Oxidativo/fisiologia , Fosfolipídeos/administração & dosagem , Fosfolipídeos/química , Líquido Sinovial/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia
18.
J Pineal Res ; 66(3): e12560, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30648758

RESUMO

The hormone melatonin has many properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose-dependently inhibits tumor necrosis factor-α (TNF-α) and interleukin (IL)-1ß expression through the PI3K/AKT, ERK, and NF-κB signaling pathways. We also identified that melatonin inhibits TNF-α and IL-1ß production by upregulating miR-3150a-3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast-like synoviocytes confirmed that the MT1 receptor is needed for the anti-inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen-induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF-α and IL-1ß production through downregulation of the PI3K/AKT, ERK, NF-κB signaling pathways, as well as miR-3150a-3p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.


Assuntos
Artrite Reumatoide/metabolismo , Fibroblastos/efeitos dos fármacos , Interleucina-1beta/biossíntese , Melatonina/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo
19.
BMC Complement Altern Med ; 19(1): 2, 2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606189

RESUMO

BACKGROUND: Saururus chinensis leaves have been used as traditional medicine in Korea for pain, intoxication, edema, and furuncle. According to previous reports, these leaves exert renoprotective, neuroprotective, and antioxidant effects by attenuating inflammatory responses. However, the beneficial effect of Saururus chinensis leaves on arthritis has not been elucidated. Thus, we evaluated the water extract of Saururus chinensis leaves (SHW) using type II collagen-induced arthritis (CIA) mice models. METHODS: Quantitative analysis of major components from SHW was performed by HPLC. Arthritis was induced by injection of type II collagen. Each group was orally administered SHW (100 mg/kg and 500 mg/kg). Methotrexate (MTX) was used as a positive control. Serum levels of interleukin-6, TNF-alpha, and type II collagen IgG in the animal models were measured using ELISA. Histological features were observed by H&E staining. RESULTS: Quantitative analysis of SHW showed the contents as 56.4 ± 0.52 mg/g of miquelianin, 7.75 ± 0.08 mg/g of quercetin 3-O-(2"-O-ß -glucopyranosyl)-α-rhamnopyranoside, and 3.17 ± 0.02 mg/g of quercitrin. Treatment with 500 mg/kg SHW decreased the serum level of Interleukin-6 (IL-6), TNF-alpha, and collagen IgG in the CIA model. Moreover, SHW treatment diminished the swelling of hind limbs and monocyte infiltration in blood vessels in CIA animal models. The results indicate that SHW could decrease CIA-induced arthritis in vivo. CONCLUSIONS: The results indicate that SHW could be used to improving arthritis by reducing inflammatory factors (IL-6 and TNF-alpha). However, further experiments are required to determine how SHW influences signal transduction in animal models.


Assuntos
Antioxidantes/farmacologia , Artrite Experimental/metabolismo , Colágeno Tipo II/efeitos adversos , Extratos Vegetais/farmacologia , Saururaceae/química , Animais , Inflamação/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Folhas de Planta/química , Membrana Sinovial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo
20.
Br J Nutr ; 121(1): 55-62, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30360768

RESUMO

The polyphenolic extract (PE) from extra virgin olive oil (EVOO) has been shown to possess important anti-inflammatory and joint protective properties in murine models of rheumatoid arthritis (RA). This study was designed to evaluate the effects of PE on IL-1ß-activated human synovial fibroblasts SW982 cell line. PE from EVOO treatment inhibited IL-1ß-induced matrix metalloproteases (P<0·001), TNF-α and IL-6 production (P<0·001). Similarly, IL-1ß-induced cyclo-oxygenase-2 and microsomal PGE synthase-1 up-regulations were down-regulated by PE (P<0·001). Moreover, IL-1ß-induced mitogen-activated protein kinase (MAPK) phosphorylation and NF-κB activation were ameliorated by PE (P<0·001). These results suggest that PE from EVOO reduces the production of proinflammatory mediators in human synovial fibroblasts; particularly, these protective effects could be related to the inhibition of MAPK and NF-κB signalling pathways. Taken together, PE from EVOO probably could provide an attractive complement in management of diseases associated with over-activation of synovial fibroblasts, such as RA.


Assuntos
Inflamação/tratamento farmacológico , Interleucina-1beta/farmacologia , Azeite de Oliva/química , Polifenóis/farmacologia , Membrana Sinovial/efeitos dos fármacos , Anti-Inflamatórios , Artrite Reumatoide/tratamento farmacológico , Linhagem Celular , Ciclo-Oxigenase 2/genética , Regulação para Baixo/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Inflamação/prevenção & controle , Interleucina-6/antagonistas & inibidores , Inibidores de Metaloproteinases de Matriz/farmacologia , Metaloproteinases da Matriz , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Polifenóis/análise , Polifenóis/isolamento & purificação , Prostaglandina-E Sintases/genética , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/citologia , Sinovite/prevenção & controle , Fator de Necrose Tumoral alfa/antagonistas & inibidores
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