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Effects of (±)-praeruptorin A on airway inflammation, airway hyperresponsiveness and NF-κB signaling pathway in a mouse model of allergic airway disease.

Abstract
The root of Peucedanum praeruptorum Dunn is a traditional Chinese medicine commonly used to treat asthma in China. (±)-praeruptorin A (PA) is the most abundant constituent of P. praeruptorum Dunn, the effects of which on asthma were investigated using a murine model of allergic airway disease. BALB/c mice were sensitized and challenged by ovalbumin to induce airway inflammation. PA was administered intragastrically before every OVA challenge. Airway responsiveness was measured by a lung function analysis system. The number of total leukocytes in bronchoalveolar lavage fluid was counted using a hemocytometer, and differential cell counts were determined using Diff-Quick-stained smears. Histopathology of lung tissue was analyzed by hematoxylin-eosin and Congo red staining. Levels of inflammatory mediators in bronchoalveolar lavage fluid and immunoglobulins in serum were measured by enzyme-linked immunosorbent assay. The expression of pulmonary eotaxin was detected by immunohistochemistry and reverse transcription polymerase chain reaction. The activation of NF-κB was evaluated by electrophoretic mobility shift assay and western blot analysis. Compared with model group, PA significantly reduced airway hyperresponsiveness and airway eosinophilic inflammation, improved pathologic lesion of the lungs, reduced levels of interleukin (IL)-4, IL-5, IL-13 and LTC₄ in bronchoalveolar lavage fluid and immunoglobulin (Ig) E in serum, and inhibited eotaxin protein and mRNA expression, IκBα degradation, NF-κB nuclear translocation, NF-κB DNA-binding activity and RelA/p65 phosphorylation in lung, which suggested that PA can significantly suppress OVA-induced airway inflammation and airway hyperresponsiveness in mice, showing great therapeutic potential for the treatment of allergic asthma.
AuthorsYouyi Xiong, Junsong Wang, Feihua Wu, Juan Li, Linfu Zhou, Lingyi Kong
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 683 Issue 1-3 Pg. 316-24 (May 15 2012) ISSN: 1879-0712 [Electronic] Netherlands
PMID22449378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Coumarins
  • Drugs, Chinese Herbal
  • Inflammation Mediators
  • NF-kappa B
  • praeruptorin A
Topics
  • Animals
  • Anti-Asthmatic Agents (administration & dosage, chemistry, isolation & purification, therapeutic use)
  • Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, chemistry, isolation & purification, therapeutic use)
  • Asthma (drug therapy, immunology, metabolism, physiopathology)
  • Coumarins (administration & dosage, chemistry, isolation & purification, therapeutic use)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal (chemistry)
  • Female
  • Inflammation Mediators (metabolism)
  • Lung (drug effects, immunology, pathology, physiopathology)
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • NF-kappa B (metabolism)
  • Pulmonary Eosinophilia (etiology, prevention & control)
  • Random Allocation
  • Respiratory Mucosa (drug effects, immunology, metabolism, pathology)
  • Signal Transduction (drug effects)
  • Specific Pathogen-Free Organisms

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