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 (EC50) 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 2 beta-hydroxy-8 beta H-7(11)-eremophilene-12,8-olide, the angelic ester of 2 beta-hydroxy-8 alpha H-7(11)-eremophilene-12,8-olide, and the angelic ester of 2 beta-hydroxy-8 beta H-7(11)-eremophilene-12,8-olide, respectively, in the mesenteric arteries. The pD2 values were somewhat lower for all compounds in aortic segments. The vasodilation was caused by a blockage of the voltage gated calcium channels. 5-petasin, (Z)-3-methylthioacrylic ester of 2 beta-hydroxy-8 beta H-7(11)-eremophilene-12,8-olide, and the angelic ester of 2 beta-hydroxy-8 alpha H-7(11)-eremophilene-12,8-olide displayed similar potencies in inhibiting DNA synthesis in cardiomyocytes and vascular smooth muscle cells. (C) 2008 Elsevier B.V. All rights reserved.