RESUMEN
Three new lupane-type triterpenoids: 6ß,30-dihydroxybetulinic acid glucopyranosyl ester (4), 6ß,30-dihydroxybetulinic acid (5) and 6ß-hydroxybetulinic acid (6), were isolated from Licania cruegeriana Urb. along with six known compounds. Their structures were elucidated on the basis of spectroscopic methods, including IR, ESIMS, 1D- and 2D-NMR experiments, as well as by comparison of their spectral data with those of related compounds. All compounds were evaluated in vivo for their effects on the mean arterial blood pressure (MABP) and heart rate (HR) of spontaneously hypertensive rats (SHR) and also in vitro for their capacity to inhibit the human platelet aggregation. None of the isolated flavonoids 1-3 showed cardiovascular effects on SHR and among the isolated triterpenoids 4-9 only 5 and 6 produced a significant reduction in MABP (60.1% and 17.2%, respectively) and an elevation in HR (11.0% and 41.2%, respectively). Compounds 3, 4, 5 and 6 were able to inhibit human platelet aggregation induced by ADP, collagen and arachidonic acid with different selectivity profiles.
Asunto(s)
Antihipertensivos/farmacología , Chrysobalanaceae/química , Extractos Vegetales/farmacología , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Animales , Antihipertensivos/aislamiento & purificación , Presión Arterial/efectos de los fármacos , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Humanos , Masculino , Extractos Vegetales/aislamiento & purificación , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Ratas Endogámicas SHR , Triterpenos/aislamiento & purificación , Triterpenos/farmacologíaRESUMEN
Pomolic acid has recently shown hypotensive effect in rats. The purpose of this investigation was to determine the vascular effects of this triterpenoid and to examine its mode of action. Functional experiments in rat aortic rings precontracted with norepinephrine were performed to evaluate the vasorelaxant effect of pomolic acid. This triterpenoid induced a vasorelaxation (IC50 = 2.45 µM) in a concentration- and endothelium-dependent manner and showed no effect on contractions evoked by KCl (25 mM). Pre-treatment of aortic rings with L-NAME (100 µM), methylene blue (100 µM) or glibenclamide (10 µM), totally prevented the vasorelaxation induced by pomolic acid, while indomethacin (10 µM) had no effect on this response. Additionally, pomolic acid relaxation was unaffected under the muscarinic- and ß-adrenergic-receptor blocked ensured for atropine and propanolol respectively (10 µM each). In contrast, the vasorelaxant effect of pomolic acid was abolished under the purinergic-receptor blocked ensured for suramin (10 µM). Finally, apyrase (0.8 U/ml) an enzyme which hydrolyses ATP and ADP did not affect pomolic acid relaxation. In summary, pomolic acid has a potent endothelium-dependent vasorelaxant effect, possibly acting through the direct activation of endothelial purinergic receptors via NO-cGMP signaling pathway, which could be part of the mechanism underlying its hypotensive effect.