Bronchodilator activity of Phymatodes scolopendria (Burm.) Ching and its bioactive constituent

Abstract

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 μg/ml, or carbachol (EC 50 = 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 (EC 50 = 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 (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.