Potent suppressive effects of 3-O-methylquercetin 5,7,3′,4′-O- tetraacetate on ovalbumin-induced airway hyperresponsiveness

Jiunn Song Jiang, Hui Chi Chien, Chien Ming Chen, Chun Nan Lin, Wun Chang Ko

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We investigated the suppressive effects of 3-O-methylquercetin 5,7,3′,4′-O-tetraacetate (QMTA), a more-potent phosphodiesterase (PDE)3/4 inhibitor than quercetin 3-O-methyl ether (3-MQ), which has been reported to have the potential for treating asthma, against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR). The IC50 value of QMTA for PDE3 was significantly less than that for PDE4. According to the Lineweaver-Burk analysis, QMTA (1-10 μM) competitively inhibited PDE3 and PDE4 activities. The Ki values were 0.9 ± 0.3 (n = 5) and 3.9 + 0.5 (n = 5) μM, respectively, which significantly differed from each other, suggesting that QMTA has higher affinity for PDE3 than for PDE4. QMTA (3-10 μM) concentration-dependently relaxed the baseline level, and significantly inhibited cumulative OVA (10-100 μg/mL)-induced contractions in isolated sensitized guinea pig trachealis suggesting that QMTA has bronchodilator and inhibiting effects on mast cell degranulation. After the secondary challenge, the AHR was measured in unrestrained OVA-sensitized mice, with nebulized methacholine (MCh, 6.25-50 mg/ mL), by barometric plethysmography using a whole-body Plethysmograph. In the present results, QMTA (3-10 μmol/kg, i.p.) dose-dependently attenuated the enhanced pause (Penh) value induced by MCh (25-50 mg/mL). QMTA (3-10 μmol/kg, i.p.) also significantly inhibited total inflammatory cells, macrophages, neutrophils, lymphocytes, and eosinophils in BALF after determination of Penh values. It also significantly suppressed the release of interleukin (IL)-2, IL-4, IL-5, IFN-γ, and TNF-α, with the exception that 3 μmol/kg QMTA did not suppress the releases of IL-5. QMTA even at 1 μmol/kg significantly inhibited eosinophils, IL-2, and TNF-α. In conclusion, our results strongly suggest that QMTA has greater potential than 3-MQ for the treatment of asthma.

Original languageEnglish
Pages (from-to)1156-1162
Number of pages7
JournalPlanta Medica
Volume73
Issue number11
DOIs
Publication statusPublished - Sep 2007

Fingerprint

ovalbumin
Ovalbumin
interleukin-5
Interleukin-5
asthma
eosinophils
interleukin-2
Eosinophils
Interleukin-2
Asthma
Phosphodiesterase 3 Inhibitors
Plethysmography
bronchodilators
Phosphodiesterase 4 Inhibitors
Cell Degranulation
Lymphocytes
Methacholine Chloride
Macrophages
Bronchodilator Agents
Phosphoric Diester Hydrolases

Keywords

  • 3-o-methylquercetin 5,7,3′,4′-o-tetraacetate
  • Asthma
  • Cytokines
  • Inflammatory cells
  • Ovalbumin
  • Phosphodiesterase inhibitor

ASJC Scopus subject areas

  • Plant Science
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Potent suppressive effects of 3-O-methylquercetin 5,7,3′,4′-O- tetraacetate on ovalbumin-induced airway hyperresponsiveness. / Jiang, Jiunn Song; Chien, Hui Chi; Chen, Chien Ming; Lin, Chun Nan; Ko, Wun Chang.

In: Planta Medica, Vol. 73, No. 11, 09.2007, p. 1156-1162.

Research output: Contribution to journalArticle

Jiang, Jiunn Song ; Chien, Hui Chi ; Chen, Chien Ming ; Lin, Chun Nan ; Ko, Wun Chang. / Potent suppressive effects of 3-O-methylquercetin 5,7,3′,4′-O- tetraacetate on ovalbumin-induced airway hyperresponsiveness. In: Planta Medica. 2007 ; Vol. 73, No. 11. pp. 1156-1162.
@article{3e56afaf8d6c45c8b533380e33595095,
title = "Potent suppressive effects of 3-O-methylquercetin 5,7,3′,4′-O- tetraacetate on ovalbumin-induced airway hyperresponsiveness",
abstract = "We investigated the suppressive effects of 3-O-methylquercetin 5,7,3′,4′-O-tetraacetate (QMTA), a more-potent phosphodiesterase (PDE)3/4 inhibitor than quercetin 3-O-methyl ether (3-MQ), which has been reported to have the potential for treating asthma, against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR). The IC50 value of QMTA for PDE3 was significantly less than that for PDE4. According to the Lineweaver-Burk analysis, QMTA (1-10 μM) competitively inhibited PDE3 and PDE4 activities. The Ki values were 0.9 ± 0.3 (n = 5) and 3.9 + 0.5 (n = 5) μM, respectively, which significantly differed from each other, suggesting that QMTA has higher affinity for PDE3 than for PDE4. QMTA (3-10 μM) concentration-dependently relaxed the baseline level, and significantly inhibited cumulative OVA (10-100 μg/mL)-induced contractions in isolated sensitized guinea pig trachealis suggesting that QMTA has bronchodilator and inhibiting effects on mast cell degranulation. After the secondary challenge, the AHR was measured in unrestrained OVA-sensitized mice, with nebulized methacholine (MCh, 6.25-50 mg/ mL), by barometric plethysmography using a whole-body Plethysmograph. In the present results, QMTA (3-10 μmol/kg, i.p.) dose-dependently attenuated the enhanced pause (Penh) value induced by MCh (25-50 mg/mL). QMTA (3-10 μmol/kg, i.p.) also significantly inhibited total inflammatory cells, macrophages, neutrophils, lymphocytes, and eosinophils in BALF after determination of Penh values. It also significantly suppressed the release of interleukin (IL)-2, IL-4, IL-5, IFN-γ, and TNF-α, with the exception that 3 μmol/kg QMTA did not suppress the releases of IL-5. QMTA even at 1 μmol/kg significantly inhibited eosinophils, IL-2, and TNF-α. In conclusion, our results strongly suggest that QMTA has greater potential than 3-MQ for the treatment of asthma.",
keywords = "3-o-methylquercetin 5,7,3′,4′-o-tetraacetate, Asthma, Cytokines, Inflammatory cells, Ovalbumin, Phosphodiesterase inhibitor",
author = "Jiang, {Jiunn Song} and Chien, {Hui Chi} and Chen, {Chien Ming} and Lin, {Chun Nan} and Ko, {Wun Chang}",
year = "2007",
month = "9",
doi = "10.1055/s-2007-981587",
language = "English",
volume = "73",
pages = "1156--1162",
journal = "Planta Medica",
issn = "0032-0943",
publisher = "Georg Thieme Verlag",
number = "11",

}

TY - JOUR

T1 - Potent suppressive effects of 3-O-methylquercetin 5,7,3′,4′-O- tetraacetate on ovalbumin-induced airway hyperresponsiveness

AU - Jiang, Jiunn Song

AU - Chien, Hui Chi

AU - Chen, Chien Ming

AU - Lin, Chun Nan

AU - Ko, Wun Chang

PY - 2007/9

Y1 - 2007/9

N2 - We investigated the suppressive effects of 3-O-methylquercetin 5,7,3′,4′-O-tetraacetate (QMTA), a more-potent phosphodiesterase (PDE)3/4 inhibitor than quercetin 3-O-methyl ether (3-MQ), which has been reported to have the potential for treating asthma, against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR). The IC50 value of QMTA for PDE3 was significantly less than that for PDE4. According to the Lineweaver-Burk analysis, QMTA (1-10 μM) competitively inhibited PDE3 and PDE4 activities. The Ki values were 0.9 ± 0.3 (n = 5) and 3.9 + 0.5 (n = 5) μM, respectively, which significantly differed from each other, suggesting that QMTA has higher affinity for PDE3 than for PDE4. QMTA (3-10 μM) concentration-dependently relaxed the baseline level, and significantly inhibited cumulative OVA (10-100 μg/mL)-induced contractions in isolated sensitized guinea pig trachealis suggesting that QMTA has bronchodilator and inhibiting effects on mast cell degranulation. After the secondary challenge, the AHR was measured in unrestrained OVA-sensitized mice, with nebulized methacholine (MCh, 6.25-50 mg/ mL), by barometric plethysmography using a whole-body Plethysmograph. In the present results, QMTA (3-10 μmol/kg, i.p.) dose-dependently attenuated the enhanced pause (Penh) value induced by MCh (25-50 mg/mL). QMTA (3-10 μmol/kg, i.p.) also significantly inhibited total inflammatory cells, macrophages, neutrophils, lymphocytes, and eosinophils in BALF after determination of Penh values. It also significantly suppressed the release of interleukin (IL)-2, IL-4, IL-5, IFN-γ, and TNF-α, with the exception that 3 μmol/kg QMTA did not suppress the releases of IL-5. QMTA even at 1 μmol/kg significantly inhibited eosinophils, IL-2, and TNF-α. In conclusion, our results strongly suggest that QMTA has greater potential than 3-MQ for the treatment of asthma.

AB - We investigated the suppressive effects of 3-O-methylquercetin 5,7,3′,4′-O-tetraacetate (QMTA), a more-potent phosphodiesterase (PDE)3/4 inhibitor than quercetin 3-O-methyl ether (3-MQ), which has been reported to have the potential for treating asthma, against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR). The IC50 value of QMTA for PDE3 was significantly less than that for PDE4. According to the Lineweaver-Burk analysis, QMTA (1-10 μM) competitively inhibited PDE3 and PDE4 activities. The Ki values were 0.9 ± 0.3 (n = 5) and 3.9 + 0.5 (n = 5) μM, respectively, which significantly differed from each other, suggesting that QMTA has higher affinity for PDE3 than for PDE4. QMTA (3-10 μM) concentration-dependently relaxed the baseline level, and significantly inhibited cumulative OVA (10-100 μg/mL)-induced contractions in isolated sensitized guinea pig trachealis suggesting that QMTA has bronchodilator and inhibiting effects on mast cell degranulation. After the secondary challenge, the AHR was measured in unrestrained OVA-sensitized mice, with nebulized methacholine (MCh, 6.25-50 mg/ mL), by barometric plethysmography using a whole-body Plethysmograph. In the present results, QMTA (3-10 μmol/kg, i.p.) dose-dependently attenuated the enhanced pause (Penh) value induced by MCh (25-50 mg/mL). QMTA (3-10 μmol/kg, i.p.) also significantly inhibited total inflammatory cells, macrophages, neutrophils, lymphocytes, and eosinophils in BALF after determination of Penh values. It also significantly suppressed the release of interleukin (IL)-2, IL-4, IL-5, IFN-γ, and TNF-α, with the exception that 3 μmol/kg QMTA did not suppress the releases of IL-5. QMTA even at 1 μmol/kg significantly inhibited eosinophils, IL-2, and TNF-α. In conclusion, our results strongly suggest that QMTA has greater potential than 3-MQ for the treatment of asthma.

KW - 3-o-methylquercetin 5,7,3′,4′-o-tetraacetate

KW - Asthma

KW - Cytokines

KW - Inflammatory cells

KW - Ovalbumin

KW - Phosphodiesterase inhibitor

UR - http://www.scopus.com/inward/record.url?scp=35348836037&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35348836037&partnerID=8YFLogxK

U2 - 10.1055/s-2007-981587

DO - 10.1055/s-2007-981587

M3 - Article

C2 - 17823872

AN - SCOPUS:35348836037

VL - 73

SP - 1156

EP - 1162

JO - Planta Medica

JF - Planta Medica

SN - 0032-0943

IS - 11

ER -