S-petasin and butterbur lactones dilate vessels through blockage of voltage gated calcium channels and block DNA synthesis

Eur J Pharmacol. 2008 Sep 28;593(1-3):79-86. doi: 10.1016/j.ejphar.2008.07.004. Epub 2008 Jul 10.

Abstract

Eremophilanlactones isolated from roots of Petasites hybridus (L.) G.M. et Sch. (Asteraceae) and S-petasin have vasodilatory effects with pD(2) -log (EC(50)) values of 6.01+/-0.08, 5.24+/-0.10, 4.74+/-0.13, and 5.43+/-0.06 for S-petasin, the (Z)-3-methylthioacrylic ester of 2beta-hydroxy-8betaH-7(11)-eremophilene-12,8-olide, the angelic ester of 2beta-hydroxy-8alphaH-7(11)-eremophilene-12,8-olide, and the angelic ester of 2beta-hydroxy-8betaH-7(11)-eremophilene-12,8-olide, respectively, in the mesenteric arteries. The pD(2) values were somewhat lower for all compounds in aortic segments. The vasodilation was caused by a blockage of the voltage gated calcium channels. S-petasin, (Z)-3-methylthioacrylic ester of 2beta-hydroxy-8betaH-7(11)-eremophilene-12,8-olide, and the angelic ester of 2beta-hydroxy-8alphaH-7(11)-eremophilene-12,8-olide displayed similar potencies in inhibiting DNA synthesis in cardiomyocytes and vascular smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Aorta, Thoracic / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Cells, Cultured
  • DNA / biosynthesis
  • Data Interpretation, Statistical
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • In Vitro Techniques
  • Lactones / pharmacology*
  • Male
  • Mesenteric Arteries / drug effects
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Myocardial Contraction / drug effects
  • Myocytes, Cardiac / drug effects
  • Myocytes, Smooth Muscle / drug effects
  • Nucleic Acid Synthesis Inhibitors / pharmacology*
  • Petasites / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Sesquiterpenes / pharmacology*
  • Thapsigargin / pharmacology
  • Vasodilator Agents / pharmacology*

Substances

  • Calcium Channel Blockers
  • Lactones
  • Nucleic Acid Synthesis Inhibitors
  • Sesquiterpenes
  • Vasodilator Agents
  • Thapsigargin
  • DNA
  • petasin