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

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.

• Authors: You-yi Xiong, Jun-song Wang, Fei-hua Wu, Juan Li, Ling-yi Kong
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 14 Issue 4 Pg. 392-400 (Dec 2012) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 22974581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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