Abstract
Persistent inflammatory reactions promote mucosal damage and cause dysfunction, such as pain, swelling, seizures, and fever. Therefore, in this study, in order to explore the anti-inflammatory effect of 6-methylcoumarin (6-MC) and suggest its availability, macrophages were stimulated with lipopolysaccharide (LPS) to conduct an in vitro experiment. The effects of 6-MC on the production and levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α) and inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) in LPS-stimulated RAW 264.7 cells were examined. The results showed that 6-MC reduced the levels of NO and PGE2 without being cytotoxic. In addition, it was demonstrated that the increase in the expression of pro-inflammatory cytokines caused by LPS stimulation, was decreased in a concentration-dependent manner with 6-MC treatment. Moreover, Western blot results showed that the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which increased with LPS treatment, were decreased by 6-MC treatment. Mechanistic studies revealed that 6-MC reduced the phosphorylation of the mitogen-activated protein kinase (MAPK) family and IκBα in the MAPK and nuclear factor-kappa B (NF-κB) pathways, respectively. These results suggest that 6-MC is a potential therapeutic agent for inflammatory diseases that inhibits inflammation via the MAPK and NF-κB pathways.
Highlights
The inflammatory reaction is an essential defense mechanism that protects the body during pathogen invasion or tissue damage and can be described as an acute or chronic inflammatory reaction according to the action and period of occurrence [1,2]
Nuclear factor-kappa B (NF-κB) pathways, respectively. These results suggest that 6-MC is a potential therapeutic agent for inflammatory diseases that inhibits inflammation via the mitogenactivated protein kinase (MAPK) and NF-κB pathways
In the acute inflammatory reaction, as macrophages are activated by antigens, pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)), and inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2 )) are secreted to remove foreign substances and are terminated through the process of tissue regeneration [3,4,5,6]
Summary
The inflammatory reaction is an essential defense mechanism that protects the body during pathogen invasion or tissue damage and can be described as an acute or chronic inflammatory reaction according to the action and period of occurrence [1,2]. (TLR4) [8,9] This stimulus increases the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and inflammatory mediators (NO and PGE2 ) through the activation of phosphorylation of transcription factors nuclear factor-kappa B (NF-κB) and mitogenactivated protein kinase (MAPK). These inflammatory mediators can kill bacteria or remove tumors and eventually contribute to the body’s defenses [10,11,12,13,14,15,16,17,18,19,20,21].
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