Bronchodilator activity of Phymatodes scolopendria (Burm.) Ching and its bioactive constituent.
Phymatodes scolopendria (Burm.) Ching (Polypodiaceae) is widely used in the Eastern coast of Madagascar to treat respiratory disorders. Bioassay-guided fractionation using guinea pig trachea pre-contracted with histamine to monitor the activity led to the isolation of 1,2-benzopyrone (coumarin) as the main active constituent. Effectively, it induced a concentration-dependent relaxation of the histamine with a median effective concentration (EC(50)) of 35.03 microg/ml, or carbachol (EC(50) = 33.41 microg/ml) pre-contracted guinea pig trachea, and also provoked 100% relaxation at 72.10 microg/ml. It was less active either on KCl pre-contracted trachea (EC(50) = 130.78 microg/ml) or endothelium denuded trachea (153.4 +/- 22 microg/ml). It inhibited, in a non-competitive manner, the histamine and the external calcium spasm effect on the isolated trachea but it did not significantly modify the broncho-constrictive activity of KCl. When combined with theophylline, coumarin produced a significant additive relaxing effect on pre-contracted trachea. Furthermore, its bronchodilator effect was not blocked by propranolol. In vivo, pre-treated guinea pig with coumarin showed significant resistance to histamine inhalation, with an adequate dose protecting 50% of the tested animals (AD(50)) of 75 mg/kg. These results indicate that the bronchodilator effect of coumarin is partly due to the endothelium-dependent tracheal relaxation, and may be mediated through a non-specific tracheal relaxation.
Ramanitrahasimbola
D
D
Institut Malgache de Recherches Appliquées, Antananarivo, Madagascar. soamadi@wanadoo.mg
Rakotondramanana
D A
DA
Rasoanaivo
P
P
Randriantsoa
A
A
Ratsimamanga
S
S
Palazzino
G
G
Galeffi
C
C
Nicoletti
M
M
D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D029621:Polypodiaceae / Q000737:chemistry; D011189:Potassium Chloride / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D001993:Bronchodilator Agents; D003374:Coumarins; D006633:Histamine Antagonists; D010936:Plant Extracts; D011189:Potassium Chloride; D011433:Propranolol; C030123:coumarin; D013806:Theophylline; D002122:Calcium Chloride