DA-9201 shows anti-asthmatic effects by suppressing NF-kappaB expression in an ovalbumin-induced mouse model of asthma.
Nuclear factor kappa B (NF-kappaB) 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 IgE and Th2 cytokines in plasma or bronchoalveolar lavage fluid (BALF), the percentage of eosinophils in BALF, and histopathological examination. The expression of NF-kappaB 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 hyperresponsiveness (AHR), total IgE 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 DA-9201 treatment. In addition, DA-9201 dramatically suppressed the expression of NF-kappaB 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-kappaB pathway.
Lee
Seung-Ho
SH
Research Institutes of Dong-A Pharmaceutical Company, Yongin, Korea.
Seo
Mi Jung
MJ
Choi
Seul Min
SM
Sohn
Yong Sung
YS
Kang
Kyung Koo
KK
Ahn
Byoung Ok
BO
Kwon
Jong Won
JW
Yoo
Moohi
M
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004802:Eosinophilia / Q000188:drug therapy; D000431:Ethanol / Q000737:chemistry; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012275:Oryza; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D018927:Anti-Asthmatic Agents; D016207:Cytokines; C507564:DA-9201; D016328:NF-kappa B; D010936:Plant Extracts; D007073:Immunoglobulin E; D000431:Ethanol; D010047:Ovalbumin