Relaxant effects of petasins in isolated guinea pig trachea and their structure-activity relationships

In the present study, we attempted to compare four petasins, isolated from Petasites formosanus Kitamura, and to look for structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four petasins, including petasin, isopetasin, S-petasin and S-isopetasin, concentration-dependently relaxed histamine (10 μM)-, carbachol (0.2 μM)-, KCl (30 mM)-, and leukotriene D₄ (10 nM)-induced precontractions of isolated guinea pig trachealis. The IC₅₀ values strongly showed that the relaxant effects of the sulfur-containing petasins, S-petasin and S-isopetasin, were more potent than those of non-sulfur-containing petasins, petasin and isopetasin. S-Isopetasin, with IC₅₀ values around 10 μM, selectively relaxed carbachol- and KCl-induced precontractions, and had almost no effects (IC₅₀s > 300 μM) on histamine- and leukotriene D₄-induced precontractions. However, S-petasin, with IC₅₀ values about 6-9 μM, non-selectively relaxed the precontractions induced by all these contractile agents. The influence of isomerization of either petasin to isopetasin or S-petasin to S-isopetasin on the relaxant effects is not clear.