Insight into the Mechanisms Underlying the Tracheorelaxant Activities of Harungana madagascariensis Stem Barks Aqueous Extract

Abstract

Stem bark decoction of Harungana madagascariensis is traditionally used orally to treat asthma and cough. However, no study has been reported on its effect on the airway smooth muscle. This study assesses the impacts of an aqueous extract from Harungana madagascariensis (HMAE) stem bark on the tracheal smooth muscle and investigates the related mechanisms. The activity of different concentrations of HMAE was evaluated on resting tension of isolated trachea and tracheal rings precontracted with acetylcholine (Ach, 10μM) or potassium chloride (KCl, 60mM). In addition, the effects of the preincubation of the tracheal rings with HMAE on contraction induced by Ach or KCl were evaluated. Then, several pharmacological antagonists were used to identify the related mechanisms. HMAE (1.5mg/mL, 3mg/mL, and 4.5mg/mL) significantly decreases the basal tone of tracheal rings as compared to the tone of non-incubated rings. Moreover, the extract inhibited cholinergic and high K + -induced contractions in rat trachea. Cumulative concentrations of HMAE (1-5 mg/mL) induced relaxation respectively in tracheal rings precontracted with Ach (Emax = 67.5±2.9 %; EC 50 =3.3±0.4 mg/mL) and KCl (Emax = 70.8±2.7 %; EC 50 = 3.0±0.4mg/mL). The effect of HMAE was potentiated in the presence of glibenclamide (an ATP-dependent K + -channel blocker), whereas it was inhibited by N ω -nitro-L-arginine methyl ester (300µM) a Nitric Oxide (NO) synthase antagonist, and by mequitazine (an H 1 -histaminergic antagonist, 1µM). The overall data suggest the inhibition of voltage-dependent calcium channels and receptor-operated calcium channels, the stimulation of NO production, the inhibition of H 1 -histaminic receptors, and the opening of K + -ATP channels as mechanisms involved in the relaxant effect of HMAE on the tracheal smooth muscle.