A new compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione, suppresses airway epithelial cell inflammatory responses in a murine model of asthma

H. Lee, A. R. Han, Y. Kim, S. H. Choi, E. Ko, N. Y. Lee, Jin-Hyun Jeong, S. H. Kim, Hyunsu Bae

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Clinical and experimental studies have established eosinophilia as a sign of allergic disorders. Activation of eosinophils in the airways is believed to cause epithelial tissue injury, contraction of airway smooth muscle and increased bronchial responsiveness. As part of the search for new anti-asthmatic agents produced by medicinal plants, the effects of 270 standardized medicinal plant extracts on cytokine-activated A549 human lung epithelial cells were evaluated. After several rounds of activity-guided screening, the new natural compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione (PPY), was isolated from Vitex rotundifolia L. To elucidate the mechanism by which the anti-asthmatic responses of PPY occurred in vitro, lung epithelial cells (A549 cell) were stimulated with TNF-α, IL-4 and IL-1β to induce the expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. PPY treatments reduced the expression of eotaxin, IL-8, IL-16 and VCAM-1 mRNA significantly. Additionally, PPY reduced eotaxin secretion in a dose-dependent manner and significantly inhibited eosinophil migration toward A549 medium. In addition, PPY treatment suppressed the phosphorylation of p65 and ERK1/2, suggesting that it can inhibit the MAPK/NF-κB pathway. To clarify the anti-inflammatory and anti-asthmatic effects of PPY in vivo, we examined the influence of PPY on the development of pulmonary eosinophilic inflammation in a murine model of asthma. To accomplish this, mice were sensitized and challenged with ovalbumin (OVA) and then examined for the following typical asthmatic reactions: an increase in the number of eosinophils in BALF; the presence of Th2 cytokines such as IL-4 and IL-5 in the BALF; the presence of allergen-specific IgE in the serum; and a marked influx of inflammatory cells into the lung. Taken together, our results revealed that PPY exerts profound inhibitory effects on the accumulation of eosinophils into the airways while reducing the levels of IL-4, IL-5, and IL-13 in the BALF. Therefore, these results suggest that PPY may be useful as a new therapeutic drug for the treatment of allergic asthma.

Original languageEnglish
Pages (from-to)591-603
Number of pages13
JournalInternational Journal of Immunopathology and Pharmacology
Volume22
Issue number3
DOIs
Publication statusPublished - 2009 Jan 1

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Eosinophils
Anti-Asthmatic Agents
Asthma
Epithelial Cells
Interleukin-4
Interleukin-5
Medicinal Plants
Lung
Interleukin-16
Vitex
Cytokines
Interleukin-13
Vascular Cell Adhesion Molecule-1
Plant Extracts
Ovalbumin
Eosinophilia
Chemotaxis
Therapeutics
Interleukin-8
Interleukin-1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

@article{bf99e3dd284747b395800c95b07c54b6,
title = "A new compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione, suppresses airway epithelial cell inflammatory responses in a murine model of asthma",
abstract = "Clinical and experimental studies have established eosinophilia as a sign of allergic disorders. Activation of eosinophils in the airways is believed to cause epithelial tissue injury, contraction of airway smooth muscle and increased bronchial responsiveness. As part of the search for new anti-asthmatic agents produced by medicinal plants, the effects of 270 standardized medicinal plant extracts on cytokine-activated A549 human lung epithelial cells were evaluated. After several rounds of activity-guided screening, the new natural compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione (PPY), was isolated from Vitex rotundifolia L. To elucidate the mechanism by which the anti-asthmatic responses of PPY occurred in vitro, lung epithelial cells (A549 cell) were stimulated with TNF-α, IL-4 and IL-1β to induce the expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. PPY treatments reduced the expression of eotaxin, IL-8, IL-16 and VCAM-1 mRNA significantly. Additionally, PPY reduced eotaxin secretion in a dose-dependent manner and significantly inhibited eosinophil migration toward A549 medium. In addition, PPY treatment suppressed the phosphorylation of p65 and ERK1/2, suggesting that it can inhibit the MAPK/NF-κB pathway. To clarify the anti-inflammatory and anti-asthmatic effects of PPY in vivo, we examined the influence of PPY on the development of pulmonary eosinophilic inflammation in a murine model of asthma. To accomplish this, mice were sensitized and challenged with ovalbumin (OVA) and then examined for the following typical asthmatic reactions: an increase in the number of eosinophils in BALF; the presence of Th2 cytokines such as IL-4 and IL-5 in the BALF; the presence of allergen-specific IgE in the serum; and a marked influx of inflammatory cells into the lung. Taken together, our results revealed that PPY exerts profound inhibitory effects on the accumulation of eosinophils into the airways while reducing the levels of IL-4, IL-5, and IL-13 in the BALF. Therefore, these results suggest that PPY may be useful as a new therapeutic drug for the treatment of allergic asthma.",
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A new compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione, suppresses airway epithelial cell inflammatory responses in a murine model of asthma. / Lee, H.; Han, A. R.; Kim, Y.; Choi, S. H.; Ko, E.; Lee, N. Y.; Jeong, Jin-Hyun; Kim, S. H.; Bae, Hyunsu.

In: International Journal of Immunopathology and Pharmacology, Vol. 22, No. 3, 01.01.2009, p. 591-603.

Research output: Contribution to journalArticle

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T1 - A new compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione, suppresses airway epithelial cell inflammatory responses in a murine model of asthma

AU - Lee, H.

AU - Han, A. R.

AU - Kim, Y.

AU - Choi, S. H.

AU - Ko, E.

AU - Lee, N. Y.

AU - Jeong, Jin-Hyun

AU - Kim, S. H.

AU - Bae, Hyunsu

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N2 - Clinical and experimental studies have established eosinophilia as a sign of allergic disorders. Activation of eosinophils in the airways is believed to cause epithelial tissue injury, contraction of airway smooth muscle and increased bronchial responsiveness. As part of the search for new anti-asthmatic agents produced by medicinal plants, the effects of 270 standardized medicinal plant extracts on cytokine-activated A549 human lung epithelial cells were evaluated. After several rounds of activity-guided screening, the new natural compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione (PPY), was isolated from Vitex rotundifolia L. To elucidate the mechanism by which the anti-asthmatic responses of PPY occurred in vitro, lung epithelial cells (A549 cell) were stimulated with TNF-α, IL-4 and IL-1β to induce the expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. PPY treatments reduced the expression of eotaxin, IL-8, IL-16 and VCAM-1 mRNA significantly. Additionally, PPY reduced eotaxin secretion in a dose-dependent manner and significantly inhibited eosinophil migration toward A549 medium. In addition, PPY treatment suppressed the phosphorylation of p65 and ERK1/2, suggesting that it can inhibit the MAPK/NF-κB pathway. To clarify the anti-inflammatory and anti-asthmatic effects of PPY in vivo, we examined the influence of PPY on the development of pulmonary eosinophilic inflammation in a murine model of asthma. To accomplish this, mice were sensitized and challenged with ovalbumin (OVA) and then examined for the following typical asthmatic reactions: an increase in the number of eosinophils in BALF; the presence of Th2 cytokines such as IL-4 and IL-5 in the BALF; the presence of allergen-specific IgE in the serum; and a marked influx of inflammatory cells into the lung. Taken together, our results revealed that PPY exerts profound inhibitory effects on the accumulation of eosinophils into the airways while reducing the levels of IL-4, IL-5, and IL-13 in the BALF. Therefore, these results suggest that PPY may be useful as a new therapeutic drug for the treatment of allergic asthma.

AB - Clinical and experimental studies have established eosinophilia as a sign of allergic disorders. Activation of eosinophils in the airways is believed to cause epithelial tissue injury, contraction of airway smooth muscle and increased bronchial responsiveness. As part of the search for new anti-asthmatic agents produced by medicinal plants, the effects of 270 standardized medicinal plant extracts on cytokine-activated A549 human lung epithelial cells were evaluated. After several rounds of activity-guided screening, the new natural compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione (PPY), was isolated from Vitex rotundifolia L. To elucidate the mechanism by which the anti-asthmatic responses of PPY occurred in vitro, lung epithelial cells (A549 cell) were stimulated with TNF-α, IL-4 and IL-1β to induce the expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. PPY treatments reduced the expression of eotaxin, IL-8, IL-16 and VCAM-1 mRNA significantly. Additionally, PPY reduced eotaxin secretion in a dose-dependent manner and significantly inhibited eosinophil migration toward A549 medium. In addition, PPY treatment suppressed the phosphorylation of p65 and ERK1/2, suggesting that it can inhibit the MAPK/NF-κB pathway. To clarify the anti-inflammatory and anti-asthmatic effects of PPY in vivo, we examined the influence of PPY on the development of pulmonary eosinophilic inflammation in a murine model of asthma. To accomplish this, mice were sensitized and challenged with ovalbumin (OVA) and then examined for the following typical asthmatic reactions: an increase in the number of eosinophils in BALF; the presence of Th2 cytokines such as IL-4 and IL-5 in the BALF; the presence of allergen-specific IgE in the serum; and a marked influx of inflammatory cells into the lung. Taken together, our results revealed that PPY exerts profound inhibitory effects on the accumulation of eosinophils into the airways while reducing the levels of IL-4, IL-5, and IL-13 in the BALF. Therefore, these results suggest that PPY may be useful as a new therapeutic drug for the treatment of allergic asthma.

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