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, a cumulative 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 a similar way (pEC50: 3.92±0.01 and 4.09±0.01, respectively), the 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.

Hypertension (HTA) is one of the primary risk factors in cardiovascular diseases and is considered one of the main causes of morbidity and mortality worldwide. Therapeutic alternatives focused on natural products and phytocompounds obtain more interest in the treatment of this type of disease, and species of Passiflora gender have presented scientific interest due to their chemical composition and the different bioactivities that their compounds have reported. This study aimed to evaluate the antihypertensive potential of extracts obtained from seeds of Passiflora vitifolia and Passiflora edulis f. edulis; for this, extraction was carried out by maceration with 97% ethanol of the seed flour of the two species; the extracts were characterized by qualitative and quantitative tests and UHPLC. Its cytotoxicity, in vivo antihypertensive potential, vasodilator effect, and possible mechanisms of action in vitro models were evaluated. The extracts did not show apparent toxicity, but showed a preventive effect of HTA, inhibited angiotensin-II (AT-II) contraction, and presented relaxation of contracted aortic rings with phenylephrine and KCl, and this was partially reversed in the presence of L-NAME. The results highlight the potential of these Passifloras as a source of extracts with antihypertensive capacity, having as possible mechanisms of action the synthesis of NO and inhibition or antagonism of AT-II.

Background: Some species of the Lauraceae family are known to produce secondary metabolites that have antiplatelet properties. Studies on the leaves of Nectandra amazonum Nees. have shown antiaggregant activity but the bark of this species has not been studied. Objectives: To assess the antiplatelet effect of the ethanolic fraction obtained from the bark of Nectandra amazonum Nees. [N.V. "laurel amarillo", Lauraceae] applying the "Born" turbidimetric method. Methods: The screening test compared the effects of a fraction of N. amazonum (0.1 mg/mL), acetylsalicylic acid (ASA, 0.5 mM, as reference standard) and dimethylsulphoxide (DMSO, 0.1%, as control) on human platelets stimulated with adenosine diphosphate (ADP, 2 µM), epinephrine (EPI, 1 uM (one micromolar)), collagen (COLL, 1 µg/mL) and arachidonic acid (AA, 0.2 mg/mL). Subsequently, the study focused on determining the antiaggregant potency of the N. amazonum fraction through concentration -response curves (from 1 µg/mL to 0.4 mg/ mL), obtaining pIC 50 ) values against the platelet agonists. Results: Control platelets attained the highest percentage values of aggregation (96% AA, 89% EPI, 85% COLL, and 77% ADP). The N. amazonum fraction significantly reduced the aggregation effects (6% AA, 45% EPI, 10% COLL, 21% ADP), with values close to those obtained with ASA (17% AA, 21% EPI, 10% COLL, 20% ADP). According to concentration -response curves, the pIC 50 values of the ethanolic fraction indicated the following order of potency: AA, 4.90 > ADP, 4.51 > COLL, 4.33 > EPI, 3.85. Conclusions: These results suggest that the N. amazonum Nees. ethanolic fraction elicited antiplatelet effects mainly related to the inhibition of the arachidonic acid pathway.

Background: Ayanin (3,7,4’-Tri-O-methylquercetin) and 3,7-Di-O-methylquercetin (DMQ) are the main active metabolites isolated by bioguided fractionation from Croton schiedeanus, species known popularly in Colombia as “almizclillo”, which has been studied in experimental models in rats, exerting vasodilator and antihypertensive effects. Also, when the effect of these flavonoids was studied separately, important vasodilation was observed. Objective: To evaluate whether flavonoids from Croton schiedeanus have synergistic vasodilator properties when different combinations are used in isolated aorta rings. Methods: Cumulative concentrations of ayanin (10-8 M - 6x10-5 M or 0.01 μM - 60 μM) were assayed in the absence and presence of an increasing concentration of 3,7-Di-O-methylquercetin (DMQ) (10-8 – 3x10-5 M or 0.01–30 μM) in isolated rings from Wistar rats, pre-contracted with phenylephrine. The concentration-response curve with the maximal effect was compared with that obtained by Croton schiedeanus whole ethanolic extract (10-6 – 3x10-4 g/mL). Also, this combination was assayed in the presence of the nitric oxide synthetase inhibitor L-NAME (10-4 M) and the guanylate cyclase inhibitor methylene blue (10-4 M) to assess the role of the NO/cGMP pathway in this interaction. Results: Ayanin and DMQ display a dual interaction in vascular relaxant response: agonism at higher concentration ranges (10-6 – 3x10-5 M or 1–30 μM) and antagonism at lower concentration ranges (10-8 – 3x10-7 M or 0.01–0.3 μM). The efficacy at the highest concentration was greater than that obtained by the whole extract (Emax: 98.4% vs. 33.9%). This response was decreased but not reverted in the presence of L-NAME and methylene blue. Thus, the vasodilator effect of this combination does not depend entirely on the NO/cGMP cyclic pathway. Conclusion: The combined use of appropriate concentrations of these flavonoids could represent an advantage over Croton schiedeanus whole extract for vasodilator purposes.