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J Cell Physiol ; 236(3): 1939-1949, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32730652

RESUMO

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1ß (IL-1ß) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1ß-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti-inflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.


Assuntos
Inflamação/prevenção & controle , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Triterpenos/uso terapêutico , Idoso , Animais , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Humanos , Inflamação/complicações , Interleucina-1beta/efeitos adversos , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Triterpenos/química , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
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