Hypotensive and vasorelaxant effect of Diapocynin in normotensive rats

Abstract

Nicotinamide adenine dinucleotide phosphate oxidase (NAD(P)H-oxidase) is a multicomponent enzyme system that generates superoxide anion by one-electron reduction of molecular oxygen and represents the major source of reactive oxygen species (ROS) in the vascular cells. Apocynin has been extensively used as an inhibitor of NADPH oxidase (NOX) in phagocytic cells and as an antioxidant in non-phagocytic cells. In phagocytes cells, due to the presence of myeloperoxidase, apocynin can be the converted to diapocynin, which is supposed to be the active form of this phytochemical. Moreover, apocynin was shown to induce hypotension and vasodilatation in many experimental animal models. However, there are no studies showing the effects of diapocynin on blood pressure or in vascular cells. In this present study, we used chemically synthesized diapocynin and analyzed its antioxidant capacity, effect on blood pressure and vascular reactivity. Moreover, it was evaluated the levels of nitric oxide (NO), ROS and calcium in aortic endothelial cells stimulated by diapocynin. All results were compared to apocynin. We found that diapocynin showed higher antioxidant capacity than apocynin. Apocynin and diapocynin, promoted hypotensive effects without changing the heart rate, however the effects of diapocynin were reversed faster than the effects of apocynin, which was long lasting. Diapocynin and apocynin induced endothelium dependent and independent vasodilatation, but diapocynin was less potent than apocynin regarding the capacity of induction of vasodilatation in mesenteric resistance arteries and aorta from Wistar rats. The relaxation induced by apocynin or diapocynin involves sGC and potassium channels in vascular smooth muscle cells and NOS participates of relaxation induced by apocynin or diapocynin in intact mesenteric rings. Apocynin and diapocynin increased NO and decreased ROS levels in endothelial cells, however diapocynin did not alter calcium levels in these cells. In conclusion, these results demonstrated that, similarly to apocynin, diapocynin also induces hypotensive and vasodilator effects in rats and vascular endothelium improves the diapocynin vasodilator effects by increases NO bioavailability.

Apocynin, an Inhibitor of the Nadph Oxidase Complex

“…The same author further justifies the increased inhibition of NADPH oxidase due to the increased hydrophobicity of the apocynin dimer over the parent compound. These studies corroborate with that reported by Potje (2017), in which the levels of nitric oxide, ROS, and calcium in aortic endothelial cells stimulated by diapocynin by apocynin were evaluated. The results presented by the author indicated that diapocynin showed a higher antioxidant capacity than apocynin, concerning the promotion of hypotensive effects without alteration of heart rate.…”

Methyl divanillate: redox properties and binding affinity with albumin of an antioxidant and potential NADPH oxidase inhibitor

“…Corroborant with these ndings, dimers as diferulic acid and diapocynin were also reported as better antioxidants compared to their monomer precursors. 11,28 It is worthy of note that MV is a methoxy-substituted catechol, a family of compound for which the potential therapeutic application is continuously increasing. The best example of this assertion is apocynin (acetovanillone).…”

“…7,10,[30][31][32] Homodimers of these methoxy-substituted catechols also have biological effects and, sometimes, superior to their precursors, as have been demonstrated to diapocynin, and divanillin. 10,11,33,34 Usually, the antioxidative efficacy of these dimers is increased.…”

“…However, DMV has structural similarity to diapocynin and divanillin, both compounds with well-known important biological effects. [10][11][12] Here, methyl divanillate was synthesized and investigated in the context of its redox properties and interaction with serum albumin, the protein responsible for transport of many endogenous and exogenous compounds in the blood circulation. 13 A comparison was made with methyl vanillate and theoretical studies were performed to elucidate the interaction of DMV with this protein.…”

Induction of axial chirality in divanillin by interaction with bovine serum albumin

“…Indeed, there is a great chance that divanillin can be as active as diapocynin regarding its biological activities. It's worth remembering that apocynin, an inhibitor of the NADPH oxidase enzymatic complex, has numerous pharmacological effects [9,10], and there is increasing evidence that diapocynin is also a promissory drug [11–13]. …”