Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, which is commonly used as a noncaloric sugar substitute in Japan and Brazil.Target:Isosteviol dose-dependently relaxed the vasopressin (10-8 M)-induced vasoconstriction in isolated aortic rings with or without endothelium. However, in the presence of potassium chloride (3×10-2 M), the vasodilator effect of isosteviol on arterial strips disappeared. Only the inhibitors specific for the ATP-sensitive potassium (KATP) channel or small conductance calcium-activated potassium (SKCa) channel inhibited the vasodilator effect of isosteviol in isolated aortic rings contracted with 10-8 M vasopressin [1]. The attenuation by isosteviol of the vasopressin- and phenylephrine-induced increase in [Ca (2+)]i was inhibited by glibenclamide, apamin and 4-aminopyridine but not by charybdotoxin. Furthermore, the inhibitory action of isosteviol on [Ca (2+)]i was blocked when A7r5 cells co-treated with glibenclamide and apamin in conjunction with 4-aminopyridine were present [2]. Isosteviol (1-100 micromol/l) inhibits angiotensin-II-induced DNA synthesis and endothelin-1 secretion. Measurements of 2'7'-dichlorofluorescin diacetate, a redox-sensitive fluorescent dye, showed an isosteviol-mediated inhibition of intracellular reactive oxygen species generated by the effects of angiotensin II [3].

[1]. Wong KL, et al. Isosteviol acts on potassium channels to relax isolated aortic strips of Wistar rat. Life Sci. 2004 Mar 26;74(19):2379-87. [2]. Wong KL, et al. Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells. Planta Med. 2004 Feb;70(2):108-12. [3]. Wong KL, et al. Antiproliferative effect of isosteviol on angiotensin-II-treated rat aortic smooth muscle cells. Pharmacology. 2006;76(4):163-9.