KMID : 0043320160390030429
|
|
Archives of Pharmacal Research 2016 Volume.39 No. 3 p.429 ~ p.436
|
|
Anti-inflammatory function of 4-tert-butylphenyl salicylate through down-regulation of the NF-kappa B pathway
|
|
Choi Yun-Hee
Na Baek-Hee Choi Yoon-Seok Rahman Saifur Kim Mi-Ri Jee Jun-Pil Shin Ji-Hoon Suh Joo-Won Yoo Jin-Cheol
|
|
Abstract
|
|
|
The salicylic acid derivative 4-tert-butylphenyl salicylate (4-TBPS) possesses anti-inflammatory activity. We demonstrated this and elucidated the mechanisms involved by using the lipopolysaccharide-stimulated Raw 264.7 mouse macrophage model. The 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blot, enzyme-linked immunosorbent assay, and reverse transcriptase-polymerase chain reaction were performed to explore 4-TBPS anti-inflammatory activity. We found that 4-TBPS decreased nitric oxide production without cytotoxic effects on macrophages and reduced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in a dose-dependent manner. Additionally, mRNA expressions of iNOS and COX-2 significantly reduced, with concentrations between 1 and 15 ¥ìg/ml. Furthermore, 4-TBPS significantly inhibited the production of pro-inflammatory cytokines including tumor necrosis factor-¥á (TNF-¥á), interleukin- (IL)-1¥â, and IL-6. Moreover, mRNA gene expression of TNF-¥á, IL-1¥â, and IL-6 was attenuated in a dose-dependent manner. 4-TBPS potently inhibited translocation of nuclear factor-¥êB (NF-¥êB) into the nucleus by degrading I¥êB kinase (I¥êB¥á) following its phosphorylation, thereby causing NF-¥êB to remain inactive. Collectively, our data indicate that 4-TBPS significantly (p < 0.01) targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, TNF-¥á, IL-1¥â, and IL-6 through downregulation of the NF-¥êB pathway. This indicates that 4-TBPS may have therapeutic potential in inflammatory disorders.
|
|
KEYWORD
|
|
Anti-inflammatory effect, 4-tert-Butylphenyl salicylate, NF-¥êB pathway, COX-2, iNOS
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|