Passiflora quadrangularis L. prevents experimental hypertension and vascular remodelling in rats exposed to nitric oxide deficit / Passiflora quadrangularis L. previene la hipertensión experimental y el remodelado vascular en ratas expuestas a déficit de óxido nítrico

Background: Passiflora quadrangularis L. is among the species used in Colombian folk medicine for hypertension, but until now it has not been studied in experimental models. Objectives: To assess the capacity of P. quadrangularis L. EtOH extract to prevent the hypertension and vascular remodelling induced by nitric oxide (NO) deficit in Wistar rats. Methods: The nitric oxide (NO) synthase inhibitor L-NAME (10 mg/kg, i.p (intraperitoneal), every 48h) was administered for seven weeks to the following groups of rats: P. quadrangularis L.75, 150 and 300 mg/kg/d, p.o. (oral route); enalapril as reference agent, 10 mg/kg/d, p.o. and vehicle as control (mixture of propylene glycol 10%, glycerine 10% and polysorbate 2%). Arterial blood pressure (BP) and heart rate (HR) were measured twice a week. After sacrifice, the aortic rings were isolated, contraction was triggered with phenylephrine (PE 10-6 M) and then the relaxant response achieved with cumulative concentrations of acetylcholine (ACh, 10-10 ­ 10-5 M) or sodium nitroprusside (SNP, 10-10 ­ 10-5 M) was assessed. Histopathologic measures of thickness/lumen ratio from both the left ventricle and aorta walls, as well as phytochemical screening, were also performed. Results: As for enalapril, all doses of P. quadrangularis L. prevented the hypertension induced by L-NAME (122±1.2 versus 155±1.3 mmHg at seventh week). P. quadrangularis L. significantly increased the relaxant effect induced by ACh in isolated aorta and decreased the thickness/lumen ratio of aorta wall specimens. Conclusions: P. quadrangularis L. prevents experimental hypertension induced in rats with nitric oxide deficits improving the endothelium vasodilatation response and protecting against vascular remodelling.

Antecedentes: Passiflora quadrangularis L. es una de las especies utilizadas en medicina tradicional en Colombia para la hipertensión pero hasta el momento no se ha evaluado en modelos experimentales. Objetivos: Evaluar la capacidad del extracto etanólico de P. quadrangularis L. para prevenir la hipertensión y el remodelado vascular inducidos por déficit de óxido nítrico (NO) en ratas Wistar. Métodos: El inhibidor de la óxido nítrico (NO) sintasa L-NAME (10 mg/kg, i.p, cada 48 h) se administró durante siete semanas a los siguientes grupos de tratamiento: P. quadrangularis L. 75, 150 y 300 mg/kg/d, p.o; Enalapril como agente de referencia, 10 mg/kg/d, p.o., y vehículo como control (mezcla de propilenglicol 10%, glicerina 10% y polisorbato 2%). Se midió la presión arterial (BP) y la frecuencia cardiaca (HR) dos veces por semana. Después del sacrificio, se aislaron los anillos aórticos, se desencadenó la contracción con fenilefrina (PE 10-6 M) y la respuesta relajante con concentraciones acumulativas de acetilcolina (ACh, 10-10 ­ 10-5 M) o nitroprusiato de sodio (SNP, 10-10 ­ 10-5 M). También se realizaron estudios histopatológicos de la relación entre el espesor y el lumen tanto en el ventrículo izquierdo como en las paredes de la aorta, así como un cribado fitoquímico. Resultados: Enalapril y todas las dosis de P. quadrangularis L. evitaron la hipertensión inducida por L-NAME (122 ± 1,2 frente a 155 ± 1,3 mm Hg a la séptima semana). P. quadrangularis L. aumentó significativamente el efecto relajante inducido por ACh en la aorta aislada y disminuyó la relación entre el espesor y la luz de los especímenes en la pared de la aorta. Conclusiones: P. quadrangularis L. previene la hipertensión experimental inducida por déficit de óxido nítrico en ratas, mejorando la respuesta del endotelio y protegiendo frente al remodelado vascular.

Involvement of GABAergic pathway in the sedative activity of apigenin, the main flavonoid from Passiflora quadrangularis pericarp

Abstract In the current study we showed that oral administration of an aqueous extract of Passiflora quadrangularis L., Passifloraceae, pericarp results in a significant prolongation of the sleep duration in mice evaluated in the ethyl ether-induced hypnosis test which indicates sedative effects. Apigenin, the main flavonoid of the extract, induced a similar sedative response when applied alone, at a dose equivalent to that found in the extract, suggesting that apigenin is mediating the sedative effects of P. quadrangularis extract. In addition, the sedative effect of apigenin was blocked by pretreatment with the benzodiazepine antagonist flumazenil (1 mg/kg), suggesting an interaction of apigenin with gamma-aminobutyric acid type A (GABAA) receptors. However, apigenin at concentrations 0.1–50 µM failed to enhance GABA-induced currents through GABAA receptors (α1β2γ2S) expressed in Xenopus oocytes. Nevertheless, based on our results, we suggest that the in vivo sedative effect of the P. quadrangularis extract and its main flavonoid apigenin maybe be due to an enhancement of the GABAergic system.

Chemical composition of hydroethanolic extracts from five species of the Passiflora genus

The diversified genus Passiflora is well distributed all over Brazil, and many species have been long used as medicinal plants, mainly against anxiety disturbances. This effect has been attributed to its rich flavonoid composition. Flavonoids’ main class, flavonoid glycosides, has presented central action, particularly as sedative-hypnotic, anxiolytic and analgesic. The objective of the present study was to make a phytochemical screening of five little studied Passiflora species, in order to evaluate their phenolic composition. For this aim, HPLC-DAD-ESI-MS/MS was used. After the preparation of the hydroalcoholic extracts, each species was evaluated by direct injection electrospray ionization (ESI) and tandem mass spectrometry. Although belonging to the same genus, the composition of each species presented particularities; this justifies the importance of studies aiming for the phenolic composition of different Passiflora species. Flavones C-glycosides were detected in all extracts, and are found as the main constituents in P. vitifolia, P. coccinea, P. bahiensis and P. sidifolia. In this last one, flavone-6,8-di-C-glycoside, apigenin-6-C-rhamnosyl-8-C-arabinoside are present in high content. Cyclopassiflosides were found in high content together with cyanogenic glycosides in P. quadrangularis, while in P. coccinea, besides flavones-C-glycosides were also found procyanidins.