Ouabain is a cardiac glycoside that has been found in S. gratus and has diverse biological activities.1,2,3,4,5,6,7 It inhibits the Na+/K+-ATPase isoforms α1β1 and α2β1 and human-ether-a-go-go (hERG), also known as Kv11.1 (IC50s = 97, 90, and 15.2 nM, respectively).2,3 Ouabain reduces the proliferation of PC3 prostate cancer and U937 lymphoma cells (EC50s = 210 and 94 nM, respectively).[4] It inhibits the cytopathic effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infected Vero cells (IC50 = <0.097 µM).[5] Ouabain (~8 µg/animal) increases systolic blood pressure in normotensive rats.[6] It has been used to induce ventricular arrythmias in vivo.[7] Formulations containing ouabain have been used in the treatment of atrial fibrillation, atrial flutter, and heart failure.
References:
[1].Jacobs, W.A., and Bigelow, N.M.Ouabain or g-strophanthinJ. Biol. Chem.96(3)647-658(1932).
[2].Katz, A., Tal, D.M., Heller, D., et al.Digoxin derivatives with enhanced selectivity for the α2 isoform of Na,K-ATPase: Effects on intraocular pressure in rabbitsJ. Biol. Chem.289(30)21153-21162(2014).
[3].Wang, L., Wible, B.A., Wan, X., et al.Cardiac glycosides as novel inhibitors of human ether-a-go-go-related gene channel traffickingJ. Pharmacol. Exp. Ther.320(2)525-534(2007).
[4].Bloise, E., Braca, A., De Tommasi, N., et al.Pro-apoptotic and cytostatic activity of naturally occurring cardenolidesCancer Chemother. Pharmacol.64(4)793-802(2009).
[5].Jeon, S., Ko, M., Lee, J., et al.Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugsAntimicrob. Agents Chemother.64(7)e00819-00820(2020).
[6].Xavier, F.E., Rossoni, L.V., Alonso, M.J., et al.Ouabain-induced hypertension alters the participation of enothelial factors in α-adrenergic responses differently in rat resistance and conductance mesenteric arteriesBr. J. Pharmacol.143(1)215-225(2004).
[7].Xue, Y.X., Aye, N.N., and Hashimoto, K.Antiarrhythmic effects of HOE642, a novel Na+-H+ exchange inhibitor, on ventricular arrhythmias in animal heartsEur. J. Pharmacol.317(2-3)309-316(1996).