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 (EC50) of 35.03 μg/ml, or carbachol (EC50 = 33.41 μg/ml) pre-contracted guinea pig trachea, and also provoked 100% relaxation at 72.10 μg/ml. It was less active either on KCl pre-contracted trachea (EC50 = 130.78 μg/ml) or endothelium denuded trachea (153.4 ± 22 μg/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 (AD50) 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.