title: Anti-inflammatory function of 4-tert-butylphenyl salicylate through down-regulation of the NF-kappa B pathway.
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 µg/ml. Furthermore, 4-TBPS significantly inhibited the production of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin- (IL)-1β, and IL-6. Moreover, mRNA gene expression of TNF-α, IL-1β, and IL-6 was attenuated in a dose-dependent manner. 4-TBPS potently inhibited translocation of nuclear factor-κB (NF-κB) into the nucleus by degrading IκB kinase (IκBα) following its phosphorylation, thereby causing NF-κB 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-α, IL-1β, and IL-6 through downregulation of the NF-κB pathway. This indicates that 4-TBPS may have therapeutic potential in inflammatory disorders.
authors: Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501-759, Korea.
authors: Yun Hee
authors: YH
authors: Choi
authors: Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501-759, Korea.
authors: Baek Hee
authors: BH
authors: Na
authors: Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501-759, Korea.
authors: Yoon Seok
authors: YS
authors: Choi
authors: Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501-759, Korea.
authors: Md
authors: M
authors: Saifur Rahman
authors: Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501-759, Korea.
authors: Mi Ri
authors: MR
authors: Kim
authors: Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501-759, Korea.
authors: Jun-Pil
authors: JP
authors: Jee
authors: Department of Complementary & Alternative Medicine, Chosun University, Gwangju, 501-759, Korea.
authors: Jihoon
authors: J
authors: Shin
authors: Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin-si, Gyeonggi-do, Korea. jwsuh@mju.ac.kr.
authors: Joo Won
authors: JW
authors: Suh
authors: Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501-759, Korea. jcyu@chosun.ac.kr.
authors: Jin Cheol
authors: JC
authors: Yoo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation; D051550:I-kappa B Kinase / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D012459:Salicylates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012459:Salicylates; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; C000618316:4-tert-butylphenyl salicylate
keywords: 4-tert-Butylphenyl salicylate; Anti-inflammatory effect; COX-2; NF-κB pathway; iNOS