Mechanism of anti-inflammatory activity of umbelliferone 6-carboxylic acid isolated from Angelica decursiva |
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Authors: | Md. Nurul Islam Ran Joo Choi Seong Eun Jin Yeong Shik Kim Bo Ra Ahn Dafang Zhao Hyun Ah Jung Jae Sue Choi |
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Affiliation: | 1. Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea;2. Natural Products Research Institute and College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea;3. Department of Food Science and Human Nutrition and Jeonju Makgeolli Research Center, Chonbuk National University, Jeonju 561-756, Republic of Korea;4. Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Republic of Korea |
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Abstract: | Aims of the studyWe 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.MethodsThe 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.ResultsUMC 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 705.1 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.ConclusionThe 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. |
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Keywords: | Umbelliferone 6-carboxylic acid Anti-inflammatory NO NF-κB RAW 264.7 cells Angelica decursiva |
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