VASCULAR MECHANISMS OF MONODESMOSIDIC TRITERPENE SAPONINS ISOLATED FROM Passiflora quadrangularis L. MECANISMOS VASCULARES DE SAPONINAS TRITERPÉNICAS MONODESMOSÍDICAS AISLADAS DE Passiflora quadrangularis L

Background: Passiflora quadrangularis L. has antihypertensive and anxiolytic properties observed in experimental models. Objectives: The aim of this work was to establish the vascular effects exerted by two known monodesmosidic triterpene saponins, 3-O-β-D-glucopyranosyloleanolic acid (Compound 1) (not previously described for this plant) and, 3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl] oleanolic acid (Compound 2), isolated from the ethanolic extract of Passiflora quadrangularis L. leaves. Methods: The structural elucidation was achieved by Nuclear Magnetic Resonance (NMR) experiments and High-Resolution Mass Spectrometry (HRMS). Aortic rings from Wistar rats, previously stimulated with phenylephrine (PE, 1μM) and washed, were exposed to cumulatively concentrations of compound 1 and compound 2 (10 to 400 μM). Ethanolic extract from leaves of P. quadrangularis L. (10 to 320 μg/ mL) and clonidine (1nM to 100μM) were also used for comparison. Concentration response curves of compounds 1 and 2 were examined in presence and absence of: endothelium, the alpha-2 antagonist yohimbine (1 and 100 μM), the alpha non selective antagonist phentolamine (1μM), the alpha-1 antagonist prazosin (1μM) and the calcium channel blocker verapamil (10 and 100 μM). In addition, cumulatively response curve of acetylcholine (ACh, 10nM to 10μM) and sodium nitroprusside (SNP, 1nM to 100μM) were assayed in rings precontracted with compounds 1 and 2 (400 μM). Results: Compounds 1 and 2 elicited a vasoconstriction response in intact aorta rings in similar way (pEC50: 3.92±0.01 and 4.09±0.01, respectively), effect that did not change in denuded rings (pEC50: 3.90±0.01 and 4.11±0.01). The potency order (pEC50) of compounds 1 and 2 decreased according to the following: verapamil (3.53±0.01 and 3.90±0.02; p<0.05) < yohimbine (3.65±0.01 and 3.94±0.02; p<0.05) < prazosin (3.86±0.01 and 4.30±0.02) < phentolamine (4.05±0.02 and 4.05±0.01). SNP but not ACh, was able to decrease the vasopressor effect of compounds 1 and 2 (pIC50: 8.61±0.01 and 8.24 ± 0.15, respectively). Conclusions: Compounds 1 and 2 are key metabolites responsible for the ex vivo vasoconstrictor response induced by P. quadrangularis L. Activation of voltage-dependent calcium channels and/or α2-adrenergic receptors stimulation could be mechanisms implicated.