7-Acetoxycoumarin Inhibits LPS-Induced Inflammatory Cytokine Synthesis by IκBα Degradation and MAPK Activation in Macrophage Cells

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-07, Vol.25 (14), p.3124
• Main Authors: Park, Taejin, Park, Jin-Soo, Sim, Ji Han, Kim, Seung-Young
• Format: Article
• Language: English
• Subjects: 7-acetoxycoumarin; Acetylation; Animals; anti-inflammatory; Anti-inflammatory agents; c-Jun protein; Cell activation; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - pharmacology; Cyclooxygenase-2; Cytokines; Cytokines - biosynthesis; Enzymes; Extracellular signal-regulated kinase; Flowers & plants; IL-1β; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Inflammatory diseases; Interleukin 6; JNK protein; Kinases; Lipopolysaccharides; Lipopolysaccharides - toxicity; Macrophages; Macrophages - metabolism; Macrophages - pathology; MAP kinase; MAP Kinase Signaling System - drug effects; Mice; mRNA; NF-KappaB Inhibitor alpha - metabolism; NF-κB protein; Nitric-oxide synthase; Phosphorylation; Prostaglandin E2; Protein kinase; Proteins; Proteolysis - drug effects; RAW 264.7 Cells; Signal transduction; Transcription factors; Tumor necrosis factor-α; umbelliferone
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25143124

Acetylation involves the chemical introduction of an acetyl group in place of an active hydrogen group into a compound. In this study, we synthesized 7-acetoxycoumarin (7AC) from acetylation of umbelliferone (UMB). We examined the anti-inflammatory properties of 7AC in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. The anti-inflammatory activity of 7AC on viability of treated cells was assessed by measuring the level of expression of NO, PGE and pro-inflammatory cytokines, namely interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in 7AC-treated RAW 264.7 macrophages. The 7AC was nontoxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition, its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner and concomitantly decreased the protein and mRNA expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, the levels of the phosphorylation of mitogen-activated protein kinase (MAPK) family proteins such as extracellular signal-regulated kinase (ERK), c-Jun -terminal kinase (JNK), p38 and nuclear factor kappa B (NF-κB) were reduced by 7AC. In conclusion, we generated an anti-inflammatory compound through acetylation and demonstrated its efficacy in cell-based in vitro assays.