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

Abstract

AIMS OF THE STUDY:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Md Nurul Islam, Ran Joo Choi, Seong Eun Jin, Yeong Shik Kim, Bo Ra Ahn, Dafang Zhao, Hyun Ah Jung, Jae Sue Choi
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 144 Issue 1 Pg. 175-81 (Oct 31 2012) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 22981803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Lipopolysaccharides
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Umbelliferones
• umbelliferone 6-carboxylic acid
• Nitric Oxide
• Carrageenan
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• Dinoprostone

Topics

• Angelica
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Carrageenan
• Cell Line
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Edema (chemically induced, drug therapy, pathology)
• Inflammation (metabolism)
• Lipopolysaccharides
• Male
• Mice
• Mice, Inbred ICR
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Phytotherapy
• Tumor Necrosis Factor-alpha (metabolism)
• Umbelliferones (pharmacology, therapeutic use)