Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 19 4 2020 08 25 386 396 Javad Boskabadi Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AND Department of Clinical Pharmacy, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran Saeideh Saadat Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran Mohammad Hosein Boskabady Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AND Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2019 12 06 2020 03 14 This study was conducted to evaluate the possible mechanisms of the relaxant effects of hydroalcoholic extract of Plantago major (P. major) on tracheal smooth muscle (TSM) in rats. The effects of cumulative concentrations of P. major (5, 10, 20 and 40 mg/mL) and theophylline (0.2, 0.4, 0.6 and 0.8 mM) were evaluated on pre-contracted TSM with 10 μΜ methacholine or 60 mM KCl. To determine the possible mechanisms, the relaxant effect of the plant was also examined on incubated TSM with atropine, indomethacin, chlorpheniramine, glibenclamide, diltiazem, papaverine, and propranolol. The results indicated concentration-dependent relaxant effects for P. major in non-incubated TSM contracted by methacholine or KCl. There was no statistically significant difference in the relaxant effects of P. major between non-incubated and incubated tissues with indomethacin, papaverine, and propranolol. However, the relaxant effects of P. major in incubated tissues with atropine (p<0.01 to p<0.001), chlorpheniramine (p<0.05 to p<0.001), glibenclamide (p<0.05), or diltiazem (p<0.01) were significantly lower than non-incubated TSM. P. major indicated relatively potent relaxant effects which were lower than those of theophylline. Muscarinic and histamine (H1) receptors inhibition, as well as calcium channel blocking and potassium channel opening effects are suggested to contribute to the TSM relaxant effect of the plant.   https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2626