Histamine (H1) Receptors, Cyclooxygenase Pathway and Nitric Oxide Formation Involved in Rat Tracheal Smooth Muscle Relaxant Effect of Berberine

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 #x3BC;g/mL) were added on precontracted TSM by methacholine or KCl in nonincubated or incubated tissues with atropine, chlorpheniramine, propranolol, diltiazem, glibenclamide, indomethacin, LNGnitro arginine methyl ester (LNAME) 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 nonincubated tissues. Berberine showed significant and concentrationdependent relaxant effects in nonincubated tissues contracted by KCl and methacholine (p lt;0.01 to p lt;0.001). There was no significant difference in the relaxant effects of berberine between nonincubated and incubated tissues with atropine, propranolol, diltiazem, glibenclamide, and papaverine. The relaxant effects of second concentrations of berberine in incubated tissues with LNAME, its three lower concentration in incubated tissues with chlorpheniramine and its all concentrations in incubated tissues with indomethacin were significantly lower than nonincubated tissues (p lt;0.05 to p lt;0.001). The EC50 values of berberine in incubated tissues with chlorpheniramine was significantly higher than the nonincubated condition (p lt;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.