Viscum album L. mother tinctures modulate Na+/K+ ATPase activity and expression, and promote endothelium-dependent vasodilation via SK channel and nitric oxide signalling

Our data demonstrated that VAMTs exhibit no cytotoxic effects, except for the VAMT derived from <i>Quercus petraea</i>, and do not induce oxidative stress in <i>in vitro</i> assays. Regarding molecular targets, distinct profiles were observed: the VAMT derived from A. alba (summer harvest) reduced Na⁺/K⁺- ATPase expression and activity in the cellular model, whereas all winter VAMTs reduced only the expression of this enzyme. The winter VAMT from <i>P. sylvestris</i> (VAMT PW) elicited vasodilation in resistance arteries from hypertensive rats. This vasodilatory effect appears to be mediated by the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signalling pathway and the subsequent activation of small conductance calcium-activated potassium channels. These data support the efficacy of VAMT PW and emphasise the impact of the host tree and season for optimizing antihypertensive potential of <i>V. album</i> samples in the context of traditional mistletoe medicine.