Relaxant Effects of Petasins in Isolated Guinea Pig Trachea and Their Structure-Activity Relationships

Abstract

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.

References

• 1 Bickle  D,, Röder  T,, Bestmann  H J,, Brune  K.. Identification and characterization of inhibitors of peptido-leukotriene-synthesis from Petasites hybridus. .  Planta Medica. 1994;;  60 318-22
• 2 Sasaki  S I.. Taiwan Minkan Yakuyo Shoukubstsu Shi (A manual of the medicinal plants of Formosa),. Taipei:; Kobun Kan, 1924: Appendix p. 9
• 3 Lin  Y L,, Mei  C H,, Huang  S L,, Kuo  Y H.. Four new sesquiterpenes from Petasites formosanus.  Journal of Natural Products. 1998;;  61 887-90
• 4 Lin  Y L,, Ou  J C,, Chen  C F,, Kuo  Y H.. Eremophilanes from Petasites formosanus Kitamura.  Chemical Pharmaceutical Bulletin. 1998;;  46 1807-9