Vasodilation and Blood Pressure-Lowering Effect of 3-Demethyl-2-Geranyl-4-Prenylbellidifoline, a Xanthone Obtained from Garcinia achachairu, in Hypertensive Rats

Abstract

3-demethyl-2-geranyl-4-prenylbellidifoline (DGP), a natural xanthone isolated from Garcinia achachairu, has previously demonstrated remarkable diuretic and renal protective actions. The present study expands its actions on the cardiovascular system by evaluating its vasorelaxant and blood pressure-lowering effects in spontaneously hypertensive rats (SHRs). Aortic endothelium-intact (E+) preparations of SHRs pre-contracted by phenylephrine and exposed to cumulative concentrations of G. achachairu extract, fractions, and DGP exhibited a significant relaxation compared to vehicle-only exposed rings. The non-selective muscarinic receptor antagonist (atropine), the non-selective inhibitor of nitric oxide synthase (L-NAME), as well as the inhibitor of soluble guanylate cyclase (ODQ) altogether avoided DGP-induced relaxation. Tetraethylammonium (small conductance Ca²⁺-activated K⁺ channel blocker), 4-aminopyridine (a voltage-dependent K⁺ channel blocker), and barium chloride (an influx-rectifying K⁺ channel blocker) significantly reduced DGP capacity to induce relaxation without the interference of glibenclamide (an ATP-sensitive inward rectifier 6.1 and 6.2 K⁺ channel blocker). Additionally, administration of DGP, 1 mg/kg i.v., decreased the mean, systolic, and diastolic arterial pressures, and the heart rate of SHRs. The natural xanthone DGP showed promising potential as an endothelium-dependent vasorelaxant, operating through the nitric oxide pathway and potassium channels, ultimately significantly reducing blood pressure in hypertensive rats.

Keywords: bioactive; hypertension; spontaneously hypertensive rats; vasculature; xanthone.

Figure 1

Vasorelaxation induced by extract and fractions obtained from G. achachairu branches in the aorta of spontaneously hypertensive rats (SHRs). (A) MEGA. (B) EA fraction. (C) BuOH fraction. (D) DCM fraction. Statistical analyses were performed using a two-way analysis of variance followed by Bonferroni’s multiple comparison test. * p < 0.05 versus VEH.

Figure 2

Vasorelaxation induced by DGP in the aorta of spontaneously hypertensive rats (SHRs). (A) Chemical structure of DGP: 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone. (B) Concentration–response curves were determined in endothelium-intact (E+) or endothelium-denuded (E−) aortic rings. Statistical analyses were performed using a two-way analysis of variance followed by Bonferroni’s multiple comparison test. * p < 0.05 versus VEH. # p < 0.05. versus other groups. VEH: vehicle.

Figure 3

Participation of the muscarinic receptor and nitric oxide pathway in DGP-induced relaxation in spontaneously hypertensive rats (SHRs) aortic rings. (A) Effect of DGP in the absence or presence of atropine; (B) effect of DGP in the absence or presence of L-NAME; and (C) effect of DGP in the absence or presence of ODQ. Statistical analyses were performed using a two-way analysis of variance followed by Bonferroni’s multiple comparison test. * p < 0.05 versus VEH. # p < 0.05. versus other groups. DGP: 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone. VEH: vehicle.

Figure 4

Influence of K⁺ channels on the vasorelaxant effect of DGP. (A) Effect of DGP in the absence or presence of 4-AP; (B) effect of DGP in the absence or presence of glibenclamide; (C) effect of DGP in the absence or presence of TEA; (D) effect of DGP in the absence or presence of BaCl2. Statistical analyses were performed using a two-way analysis of variance followed by Bonferroni’s multiple comparison test. * p < 0.05 versus VEH. # p < 0.05 versus other groups. DGP: 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone. VEH: vehicle. 4-AP: 4-aminopyridine. TEA: tetraethylammonium. BaCl2: barium chloride.

Figure 5

Blood pressure-lowering effect of DGP in spontaneously hypertensive rats (SHRs). Statistical analyses were performed using a one-way analysis of variance followed by Bonferroni’s multiple comparison test. * p < 0.05 versus VEH. # p < 0.05 versus 0.1 mg/kg group. DGP: 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone. VEH: vehicle. (A) MAP: mean arterial pressure. (B) SAP: systolic arterial pressure. (C) DAP: diastolic arterial pressure. (D) HR: heart rate.