Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea.
J Ethnopharmacol. 2012 Oct 31;144(1):175-81. doi: 10.1016/j.jep.2012.08.048. Epub 2012 Sep 8.
We recently reported the potential antioxidant and anti-inflammatory activities of umbelliferone 6-carboxylic acid (UMC) isolated from the whole plants of Angelica decursiva. In this study, we elucidated the anti-inflammatory mechanisms of UMC in vitro and in vivo.
The inhibitory effects of UMC on the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and tumor necrosis factor-α (TNF-α), the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the activation of nuclear factor kappa B (NF-κB) were evaluated using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The reactive oxygen species (ROS) generation inhibitory activity of UMC was evaluated using t-butyl hydroperoxide (t-BHP)-induced RAW 264.7 cells. Furthermore, the in vivo anti-inflammatory activity of UMC was evaluated using carrageenan induced mouse paw edema model.
UMC dose-dependently inhibited NO and PGE(2) production by down-regulating iNOS and COX-2 protein expression in LPS-stimulated RAW 264.7 macrophages. UMC also suppressed the production of the proinflammatory cytokine TNF-α in LPS stimulated RAW 264.7 cells in a concentration dependent manner. In addition, UMC dose-dependently prevented LPS-induced nuclear translocation of NF-κB in RAW 264.7 macrophages. Furthermore, UMC exhibited the inhibitory activity against t-BHP-induced ROS generation in RAW 264.7 cells with an IC(50) value of 705.1 μg/ml. Moreover, UMC inhibited λ-carrageenan induced mouse paw edema by 70.40 and 60.20% at doses of 50 and 25 mg/kg body weight, respectively.
The combined results of this study indicate that UMC is an important anti-inflammatory constituent of A. decursiva and its anti-inflammatory effect was due to its ability to inhibit the production of inflammatory mediators via inhibition of NF-κB activation pathway.
我们最近报道了从当归全草中分离得到的伞形酮 6-羧酸（UMC）具有潜在的抗氧化和抗炎活性。本研究旨在体外和体内阐明 UMC 的抗炎机制。
采用脂多糖（LPS）刺激 RAW 264.7 细胞，评估 UMC 对一氧化氮（NO）、前列腺素 E2（PGE2）和肿瘤坏死因子-α（TNF-α）产生的抑制作用，评估 UMC 对诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）表达、核因子κB（NF-κB）活化的抑制作用。采用 t-丁基过氧化物（t-BHP）诱导 RAW 264.7 细胞，评估 UMC 抑制活性氧（ROS）生成的活性。此外，采用角叉菜胶诱导的小鼠足肿胀模型评价 UMC 的体内抗炎活性。
UMC 可剂量依赖性地下调 LPS 刺激的 RAW 264.7 巨噬细胞中 iNOS 和 COX-2 蛋白表达，从而抑制 NO 和 PGE2 的产生。UMC 还可浓度依赖性地抑制 LPS 刺激的 RAW 264.7 细胞中促炎细胞因子 TNF-α的产生。此外，UMC 可剂量依赖性地阻止 LPS 诱导的 RAW 264.7 巨噬细胞中 NF-κB 的核转位。此外，UMC 对 t-BHP 诱导的 RAW 264.7 细胞 ROS 生成具有抑制活性，IC50 值为 705.1 μg/ml。此外，UMC 可分别以 50 和 25 mg/kg 体重剂量抑制 λ-角叉菜胶诱导的小鼠足肿胀，抑制率分别为 70.40%和 60.20%。
本研究结果表明，UMC 是当归的一种重要抗炎成分，其抗炎作用可能是通过抑制 NF-κB 激活通路抑制炎症介质的产生。
