The effects of (±)-Praeruptorin A on airway inflammation, remodeling and transforming growth factor-β1/Smad signaling pathway in a murine model of allergic asthma

Int Immunopharmacol. 2012 Dec;14(4):392-400. doi: 10.1016/j.intimp.2012.08.019. Epub 2012 Sep 11.

Abstract

(±)-Praeruptorin A (PA) is a pair of coumarin enantiomers isolated from the root of Peucedanum praeruptorum Dunn (PPD), a common Chinese herbal medicine for the treatment of asthma. Considering its anti-inflammatory, anti-contractile and anti-hyperplasia activities, the effects of PA on airway inflammation and airway remodeling were investigated using a murine model of chronic asthma. Ovalbumin-sensitized BALB/c mice were challenged with ovalbumin to induce asthma every other day on eight successive weeks. PA was administered intragastrically before every ovalbumin challenge. Airway responsiveness was evaluated by a lung function analysis system 48 h after the last ovalbumin challenge. The total and differential leukocytes in bronchoalveolar lavage fluid (BALF) were counted using a hemocytometer and Diff-Quick-stained smears. Lung tissue samples were used for hematoxylin and eosin, periodic acid Schiff, Masson's trichrome and α-SMA immunohistochemistry staining. Levels of cytokines in BALF, immunoglobulin (Ig) E in serum as well as expression of TGF-β1 and Smad proteins in lung tissue were measured by enzyme-linked immunosorbent assay, immunohistochemistry or western blot analysis. Compared with the model group, PA suppressed airway inflammation, airway hyperresponsive and remodeling, reduced levels of IL-4 and IL-13 in BALF, and IgE in serum, inhibited expression of TGF-β1 and pSmad2/3, up-regulated the expression of Smad7 in lung tissue, and also increased the levels of INF-γ in BALF. These results suggested that PA significantly suppressed airway inflammation and airway remodeling induced by ovalbumin challenge, and is a potential candidate for the treatment of asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Remodeling / drug effects*
  • Animals
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / chemically induced*
  • Asthma / drug therapy
  • Budesonide / pharmacology
  • Cell Line
  • Coumarins / administration & dosage
  • Coumarins / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation / drug effects
  • Immunoglobulin E / genetics
  • Immunoglobulin E / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Macrophages / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Smad Proteins / genetics
  • Smad Proteins / metabolism*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • Anti-Asthmatic Agents
  • Coumarins
  • Smad Proteins
  • Transforming Growth Factor beta
  • praeruptorin A
  • Immunoglobulin E
  • Budesonide