S-petasin and butterbur lactones dilate vessels through blockage of voltage gated calcium channels and block DNA synthesis.
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.
Sheykhzade
Majid
M
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
Smajilovic
Sanela
S
Issa
Ali
A
Haunso
Stig
S
Christensen
Søren Brøgger
SB
Tfelt-Hansen
Jacob
J
D000818:Animals; D000831:Animals, Newborn; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D036901:Petasites / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D007783:Lactones; D019384:Nucleic Acid Synthesis Inhibitors; D012717:Sesquiterpenes; D014665:Vasodilator Agents; D019284:Thapsigargin; D004247:DNA; C418727:petasin