Mechanism of anti-inflammatory activity of umbelliferone 6-carboxylic acid isolated from Angelica decursiva

• Published in: Journal of ethnopharmacology 2012-10, Vol.144 (1), p.175-181
• Main Authors: Nurul Islam, Md, Joo Choi, Ran, Eun Jin, Seong, Shik Kim, Yeong, Ra Ahn, Bo, Zhao, Dafang, Ah Jung, Hyun, Sue Choi, Jae
• Format: Article
• Language: English
• Subjects: Angelica; Angelica decursiva; Animals; Anti-inflammatory; anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; antioxidant activity; body weight; Carrageenan; Cell Line; Cyclooxygenase 2 - metabolism; Dinoprostone - metabolism; edema; Edema - chemically induced; Edema - drug therapy; Edema - pathology; Inflammation - metabolism; inhibitory concentration 50; Lipopolysaccharides; macrophages; Male; Mice; Mice, Inbred ICR; necrosis; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB; nitric oxide; Nitric Oxide - metabolism; nitric oxide synthase; Nitric Oxide Synthase Type II - metabolism; Phytotherapy; prostaglandins; protein synthesis; RAW 264.7 cells; reactive oxygen species; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism; Umbelliferone 6-carboxylic acid; umbelliferones; Umbelliferones - pharmacology; Umbelliferones - therapeutic use
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2012.08.048

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 E2 (PGE2), 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 PGE2 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 IC50 value of 705.1μg/ml. Moreover, UMC inhibited λ-carrageenan induced mouse paw edema by 70.40 and 60.20% at doses of 50 and 25mg/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. [Display omitted]