Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 3 2019 06 08 320 331 Saeideh Saadat Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AND Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Farzaneh Naghdi Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AND Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Vahideh Ghorani Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AND Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Hassan Rakhshandeh Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Hossein Boskabady Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AND Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2018 10 31 2019 02 17 In this study we aimed to examine the relaxant effect of berberine, a compound extracted from a variety of herbs, on rat tracheal smooth muscle (TSM) and its possible mechanism(s). Cumulative concentrations of berberine (20, 65, 200 and 600 μg/mL) were added on pre-contracted TSM by methacholine or KCl in non-incubated or incubated tissues with atropine, chlorpheniramine, propranolol, diltiazem, glibenclamide, indomethacin, L-NG-nitro arginine methyl ester (L-NAME) and papaverine. The relaxant effects of theophylline (0.2, 0.4, 0.6 and 0.8 mM) as positive control and saline (1 mL) as negative control were also examined in non-incubated tissues. Berberine showed significant and concentration-dependent relaxant effects in non-incubated tissues contracted by KCl and methacholine (p<0.01 to p<0.001). There was no significant difference in the relaxant effects of berberine between non-incubated and incubated tissues with atropine, propranolol, diltiazem, glibenclamide, and papaverine. The relaxant effects of second concentrations of berberine in incubated tissues with L-NAME, its three lower concentration in incubated tissues with chlorpheniramine and its all concentrations in incubated tissues with indomethacin were significantly lower than non-incubated tissues (p<0.05 to p<0.001). The EC50 values of berberine in incubated tissues with chlorpheniramine was significantly higher than the non-incubated condition (p<0.05). Our findings reveal a relatively potent relaxant effect of berberine that is lower than the effect of theophylline. Proposed mechanisms for the relaxant effect of berberine are histamine (H1) receptor blockade, inhibition of cyclooxygenase pathways and/or nitric oxide formation. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2182 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2182/1423