Mechanisms of relaxant action of luteolin in isolated guinea pig trachea

Wun-Chang Ko, Chwen Ming Shih, I. Jung Leu, Tzu Ting Chen, Jung P. Chang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We have investigated the mechanisms of action of luteolin, a flavone found in Perilla frutescens, a Chinese herbal medicine for treating asthma. In fact, luteolin occurs mostly as a glycoside in many plant species. The tension changes of tracheal segments were isometrically recorded on a polygraph. Luteolin concentration-dependently relaxed histamine (30 μM)-, carbachol (0.2 μM)- and KCl (30 mM)-induced precontractions, and inhibited cumulative histamine- and carbachol-induced contractions in a non-competitive manner. Luteolin also concentration-dependently and non-competitively inhibited cumulative Ca 2+-induced contractions in depolarized (K+, 60 mM) guinea-pig trachealis. The nifedipine (10 μM)-remaining tension of histamine (30 μM)-induced precontractions was further relaxed by luteolin, suggesting that no matter whether VDCCs were blocked or not, luteolin may have other mechanisms of relaxant action. The relaxant effect of luteolin was unaffected by the removal of epithelium or by the presence of propranolol (1 μM), 2′,5′-dideoxyadenosine (10 μM), methylene blue (25 μM), glibenclamide (10 μM), Nω-nitro-1-arginine (20 μM), or α-chymotrypsin (1 U/mL). However, luteolin (10-20 μM) produced parallel and leftward shifts of the concentration-response curve of forskolin or nitro-prusside. Luteolin or IBMX at various concentrations (10-300 μM) concentration-dependently and significantly inhibited cAMP- and cGMP-PDE activities of the trachealis. The IC50 values of luteolin were estimated to be 32.4 and 34.6 μM, respectively. IBMX at various concentrations (10-300 μM) selectively inhibited neither cAMP-, nor cGMP-PDE activity. In contrast to IBMX, luteolin at 100 and 300 μM more potently (P <0.05) inhibited cGMP-, than cAMP-PDE activity. The above results indicate that the mechanisms of relaxant action of luteolin may be due to its inhibitory effects on both PDE activities and its reduction on [Ca2+] i of the trachealis.

Original languageEnglish
Pages (from-to)406-411
Number of pages6
JournalPlanta Medica
Volume71
Issue number5
DOIs
Publication statusPublished - May 2005

Fingerprint

Luteolin
trachea (vertebrates)
luteolin
Trachea
guinea pigs
Guinea Pigs
1-Methyl-3-isobutylxanthine
histamine
Histamine
carbachol
flavone
Carbachol
Perilla frutescens
Dideoxyadenosine
glibenclamide
propranolol
forskolin
methylene blue
Herbal Medicine
Glyburide

Keywords

  • Flavonoid
  • Guinea-pig trachea
  • Intracellular calcium
  • Luteolin
  • Phosphodiesterase

ASJC Scopus subject areas

  • Plant Science
  • Organic Chemistry
  • Drug Discovery
  • Pharmacology

Cite this

Mechanisms of relaxant action of luteolin in isolated guinea pig trachea. / Ko, Wun-Chang; Shih, Chwen Ming; Leu, I. Jung; Chen, Tzu Ting; Chang, Jung P.

In: Planta Medica, Vol. 71, No. 5, 05.2005, p. 406-411.

Research output: Contribution to journalArticle

Ko, Wun-Chang ; Shih, Chwen Ming ; Leu, I. Jung ; Chen, Tzu Ting ; Chang, Jung P. / Mechanisms of relaxant action of luteolin in isolated guinea pig trachea. In: Planta Medica. 2005 ; Vol. 71, No. 5. pp. 406-411.
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N2 - We have investigated the mechanisms of action of luteolin, a flavone found in Perilla frutescens, a Chinese herbal medicine for treating asthma. In fact, luteolin occurs mostly as a glycoside in many plant species. The tension changes of tracheal segments were isometrically recorded on a polygraph. Luteolin concentration-dependently relaxed histamine (30 μM)-, carbachol (0.2 μM)- and KCl (30 mM)-induced precontractions, and inhibited cumulative histamine- and carbachol-induced contractions in a non-competitive manner. Luteolin also concentration-dependently and non-competitively inhibited cumulative Ca 2+-induced contractions in depolarized (K+, 60 mM) guinea-pig trachealis. The nifedipine (10 μM)-remaining tension of histamine (30 μM)-induced precontractions was further relaxed by luteolin, suggesting that no matter whether VDCCs were blocked or not, luteolin may have other mechanisms of relaxant action. The relaxant effect of luteolin was unaffected by the removal of epithelium or by the presence of propranolol (1 μM), 2′,5′-dideoxyadenosine (10 μM), methylene blue (25 μM), glibenclamide (10 μM), Nω-nitro-1-arginine (20 μM), or α-chymotrypsin (1 U/mL). However, luteolin (10-20 μM) produced parallel and leftward shifts of the concentration-response curve of forskolin or nitro-prusside. Luteolin or IBMX at various concentrations (10-300 μM) concentration-dependently and significantly inhibited cAMP- and cGMP-PDE activities of the trachealis. The IC50 values of luteolin were estimated to be 32.4 and 34.6 μM, respectively. IBMX at various concentrations (10-300 μM) selectively inhibited neither cAMP-, nor cGMP-PDE activity. In contrast to IBMX, luteolin at 100 and 300 μM more potently (P <0.05) inhibited cGMP-, than cAMP-PDE activity. The above results indicate that the mechanisms of relaxant action of luteolin may be due to its inhibitory effects on both PDE activities and its reduction on [Ca2+] i of the trachealis.

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