Mechanism of the vasodilator effect of Euxanthone in rat small mesenteric arteries

Abstract

In the present work we investigated the mechanism involved in the vasodilator effect induced by euxanthone in rat small mesenteric arteries. We observed that euxanthone induced concentration-dependent vasodilatation in arteries by a mechanism independent on the release of endothelial factors, such as nitric oxide (NO) and cyclooxygenase-derived factors. In addition our results also suggest that euxanthone induced its vasodilator effect through inhibition of calcium-sensitive mechanisms activated by protein kinase C, rather than by inhibition of contractions dependent on the release of the intracellular calcium stores or by inhibition of voltage-operated calcium channels.

Mechanism of the Vasodilator Effect of Mono-oxygenated Xanthones: A Structure-Activity Relationship Study

“…As the vasoconstrictor effect of high K + is directly related to the activation of VGCCs and Ca 2+ influx [24], the results obtained with 4-hydroxyxanthone clearly demonstrated that the mechanism of action of this xanthone involves the blockage of this pathway. The participation of the inhibition of Ca 2+ influx, through the blockade of VGCCs, on the vasodilator effect of 9-xanthenone has already been reported [9,25]. Therefore, in the present work, the blockade of VGCCs is one of the likely mechanisms of action of 9-xanthenone.…”

“…Some works proposed an antiarrhythmic [6] and a protective effect against myocardial ischemia-reperfusion injury [7]. Among the main effects of xanthones on the cardiovascular system that may be noted is the antihypertensive effect that is mainly mediated by their ability to induce vasodilatation [8][9][10]. In addition, xanthones have been associated to have a protective effect against vascular endothelial cell damage [11].…”

“…In fact, some works have suggested beneficial cardiovascular effects mediated by xanthones, such as protection against cardiac reperfusion damage [7], improvement of aldehyde dehydrogenase 2 activity, prevention of nitroglycerin tolerance [19], and activation of angiotensinconverting enzyme 2 [20]. However, the major cardiovascular effect attributed to xanthones is directly related to their ability to induce vasodilation through protein kinase A activation [14] or Ca 2+ channel blockade [9,14]. In view of the potential beneficial effects of xanthones in the cardiovascular system and their multiple mechanisms of action, it is interesting to investigate the potential vasodilator activity of new xanthones and to study the structure/activity relationship of this class of polyphenols in order to shed more light on the mechanisms of their vasorelaxant effect.…”

Retracted: Euxanthone inhibits glycolysis and triggers mitochondria‐mediated apoptosis by targeting hexokinase 2 in epithelial ovarian cancer

“…For example, the neuritogenic effect of euxanthone has been noted, supporting its role in neurological disorders . Saraiva et al have reported that euxanthone could modulate the protein kinase C, and a vasodilatory role of euxanthone was shown in in vitro and in vivo studies . A recent study showed the selective cytotoxic effect of euxanthone in cancerous cells .…”

“…As shown in Figure 6B euxanthone could modulate the protein kinase C, 22 and a vasodilatory role of euxanthone was shown in in vitro and in vivo studies. 14,23,24 A recent study showed the selective cytotoxic effect of euxanthone in cancerous cells. 16 Our results show that euxanthone induced apoptosis through mitochondrial dysfunction in EOC cells.…”