DA-9201 Shows Anti-Asthmatic Effects by Suppressing NF-$\kappa$B Expression in an Ovalbumin-Induced Mouse Model of Asthma

  • Lee Seung-Ho (Research Institutes of Dong-A Pharmaceutical Company) ;
  • Seo Mi Jung (Research Institutes of Dong-A Pharmaceutical Company) ;
  • Choi Seul Min (Research Institutes of Dong-A Pharmaceutical Company) ;
  • Sohn Yong Sung (Research Institutes of Dong-A Pharmaceutical Company) ;
  • Kang Kyung Koo (Research Institutes of Dong-A Pharmaceutical Company) ;
  • Ahn Byoung Ok (Research Institutes of Dong-A Pharmaceutical Company) ;
  • Kwon Jong Won (Research Institutes of Dong-A Pharmaceutical Company) ;
  • Yoo Moohi (Research Institutes of Dong-A Pharmaceutical Company)
  • Published : 2005.12.01

Abstract

Nuclear factor kappa B (NF-$\kappa$B) regulates the expression of multiple cytokines, chemokines, and cell adhesion molecules that are involved in the pathogenesis of asthma. We investigated the anti-asthmatic effects and the mechanism of action of DA-9201, an extract of the black rice, in a mouse model of asthma. Mice immunized with ovalbumin (OVA) were administered with DA-9201 (30, 100 or 300 mg/kg) or dexamethasone (DEXA, 3 mg/kg) for 2 weeks and challenged with aerosolized OVA during the last 3 days. Anti-asthmatic effects were assessed by means of enhanced pauses, level of total lgE and Th2 cytokines in plasma or bronchoalveolar lavage fluid (BALF), the percentage of eosinophils in BALF, and histopathological examination. The expression of NF-$\kappa$B in nuclear and cytoplasmic fraction and its DNA-binding activity in lung tissues were analyzed by means of Western blotting and electrophoretic gel mobility shift assay (EMSA), respectively. DA-9201 significantly reduced airway hyperrespon-siveness (AHR), total lgE level in plasma and BALF, IL-4, IL-5, and IL-13 levels in BALF, and the percentage of eosinophils in BALF. Tissue inflammation was significantly improved by DA­9201 treatment. In addition, DA-9201 dramatically suppressed the expression of NF-$\kappa$B and its DNA-binding activity. These results suggest that DA-9201 may be useful for the treatment of asthma and its efficacy is related to suppression of NF-$\kappa$B pathway.

Keywords

References

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