Inhibition of smooth muscle contraction by magnolol and honokiol in porcine trachea

Magnolol and honokiol are the two major phenolic constituents of the plant medicine "Houpo" (Magnolia obovata), which is used in the treatment of chest tightness and asthma. The aim of this study was to investigate the influence of magnolol and honokiol on smooth muscle tone in porcine trachea. Magnolol and honokiol (0.1 - 100 muM) inhibited carbachol- and high K+-induced muscle contractions in a concentration-dependent fashion, but did not affect basal muscle tension. After washout of these pre-treatments, carbachol- and high K+-evoked muscle contractions were still abolished, suggesting that the inhibition was irreversible. Magnolol and honokiol also concentration-dependently decreased the Ca2+-dependent muscle contraction induced by high K+ depolarization. Ca2+ channel antagonists attenuated carbachol-induced muscular response by similar to30%, but did not further potentiate the inhibitory actions of magnolol and honokiol on muscle contraction. However, the inhibitory effects of magnolol and honokiol on carbachol-evoked muscular contractile response were partially reversed after removal of Ca2+ channel antagonist pretreatment. Alternatively, caffeine-elicited muscle contractions were not altered by magnolol, honokiol, and verapamil. In conclusion, the relaxant effects of magnolol and honokiol on porcine tracheal smooth muscle suggest an association with the blockade of Ca2+ influx through voltage-operated Ca2+ channels instead of Ca2+ release from intracellular Ca2+ stores. The magnolol- and honokiol-induced inhibitions on tracheal smooth muscle contraction may be relevant to the claimed therapeutic effects of the extract from magnolia bark and contribute to their pharmacological effects by acting as anti-asthmatic agents.