2-Styrylchromones Prevent IL-1 beta-Induced Pro-Inflammatory Activation of Fibroblast-like Synoviocytes while Increasing COX-2 Expression

• Tipo: Artigo em Revista Científica Internacional
• Data: 2023

Autores

Rufino, AT (Autor) Outra; Lucas, M (Autor) Outra; Silva, AMS (Autor) Outra; Ribeiro, D (Autor) Outra; Eduarda Fernandes (Autor) FFUP

Revista

Título: Pharmaceutics

Vol. 15

Página Final: 780

ISSN: 1999-4923

Editora: MDPI

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 0 Citações

Outras Informações

ID Authenticus: P-00Y-7BW

DOI: 10.3390/pharmaceutics15030780

Abstract (EN): Rheumatoid arthritis (RA) is characterized by systemic immune and chronic inflammatory features, leading to the destruction of the joints. Presently, there are no effective drugs able to control synovitis and catabolism in the process of RA. 2-Styrylchromones (2-SC) are a small group of compounds characterized by the attachment of a styryl group to the chromone core that have already been associated to a wide range of biological activities, including antioxidant and anti-inflammatory activities. The present study investigated the effect of a set of six 2-SC on the interleukin-1 beta (IL-1 beta)-induced increase of nitric oxide ((NO)-N-center dot), inducible form of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-3 (MMP-3) expression levels in human fibroblast-like synoviocytes (HFLS), pointing to the role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) activation in the process. From a set of six 2-SC, presenting hydroxy and methoxy substituents, the one presenting two methoxy substituents at C-5 and C-7 of A ring and a catechol group on B ring, significantly reduced (NO)-N-center dot production and the expression of its inducible synthase (iNOS). It also significantly reduced the catabolic MMP-3 protein expression. This 2-SC inhibited the NF-kappa B pathway by reversing the IL-1 beta - induced levels of cytoplasmatic NF-kB inhibitor alpha (I kappa B alpha), and decreasing the p65 nuclear levels, suggesting the involvement of these pathways in the observed effects. The same 2-SC significantly increased the COX-2 expression, which may indicate a negative feedback loop mechanism of action. The properties of 2-SC may be of great value in the development of new therapies with improved efficacy and selectivity towards RA, and thus deserve further exploitation and evaluation to disclose the full potential of 2-SC.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13