Department of Pharmaceutical Engineering & Biotechnology, Sunmoon University, Chungnam 31460, Korea.
Natural Product Informatics Research Center, KIST Gangneung Institute of Natural Products, Korea 9 Institute of Science and Technology (KIST), Gangwon-do 25451, Korea.
Molecules. 2020 Jul 8;25(14):3124. 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.
乙酰化涉及将乙酰基化学引入化合物中，取代活性氢基团。在这项研究中，我们通过 Umbelliferone（UMB）的乙酰化合成了 7-乙酰氧基香豆素（7AC）。我们研究了 7AC 在脂多糖（LPS）处理的 RAW 264.7 巨噬细胞中的抗炎特性。通过测量 LPS 处理的 RAW 264.7 巨噬细胞中 NO、PGE 和促炎细胞因子（即白细胞介素 1β（IL-1β）、白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达水平，评估 7AC 对处理细胞活力的抗炎活性。7AC 对细胞无毒，并以浓度依赖的方式抑制细胞因子的产生。此外，其治疗以剂量依赖的方式抑制促炎细胞因子的产生，同时降低诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的蛋白和 mRNA 表达。此外，7AC 还降低了丝裂原活化蛋白激酶（MAPK）家族蛋白如细胞外信号调节激酶（ERK）、c-Jun 末端激酶（JNK）、p38 和核因子 kappa B（NF-κB）的磷酸化水平。总之，我们通过乙酰化生成了一种抗炎化合物，并在基于细胞的体外试验中证明了其功效。
