Subacute toxicology studies on the aqueous fraction of the ethanol extract of the leaves of Cissampelos sympodialis Eichl. (Menispermaceae) in dogs

Cissampelos sympodialis Eichl. (Menispermaceae) has been investigated about its botanical, chemical, pharmacological and toxicological aspects in our laboratory. Previous acute toxicology studies demonstrated that in dogs as well as in Wistar rats, 5 g/kg, p.o., and 2 g/kg, i.p. of the aqueous fraction of the ethanol extract of the leaves of Cissampelos sympodialis (AFL), induced a significant increase in the phosphatase alkaline and gama glutamil tranferase (GGT) levels, that were completely reversed in 15 days after interruption of AFL treatment. The aim of the present work was to investigate the subacute toxicology effects induced by AFL in dogs. We used the methods proposed by Portaria 116/96 of the Secretaria Nacional de Vigilância Sanitária, which regulates studies of toxicity for phytomedicines in Brazil. Daily administration (p.o.) of AFL, 45 mg/kg/day (5 times the dose used by human beings), during 4 weeks, was devoid of any effect on haematological (haemogram and platelets) and on blood biochemical parametes. In conclusion, the present study, using dogs, demonstrated that AFL, in a popularly used dose, by human beings, was devoid of any toxicological effect

Comparison of the hypotensive effect induced by the ethanol extract of <i>Albizia inopinata</i> G. P. Lewis in normotensive and chronically L-NAME hypertensive rats

El objetivo del presente estudio fue caracterizar la respuesta hipotensora provocada por la fracción acuosa del extracto etanólico de hojas (AFL) de Albizia inopinata en ratas normotensas y hipertensas por el L-NAME (N-nitro-L-argininA metiléster). En las ratas normotensas, AFL provocó una disminución dosis-dependiente de la presión arterial, acompãnada de un aumento de la frecuencia cardíaca. Ya en el caso de las ratas hipertensas, AFL provocó una hipotensión más aguda, en tanto que las modificaciones de la frecuencia cardíaca no fueron significativas. En los anillos de la aorta, concentraciones crecientes de AFL antagonizaron las contracciones provocadas por fenilefrina y KCl; por otro lado, los valores de CI 50 para ratas normotensas fueron significantemente superiores a los obtenidos en ratas hipertensas. El efecto vasodilator de AFL parece ser claramente dependiente de la liberación de NO por el endotelio vascular. En conclusión, el presente estudio demuestra que AFL disminuye la presión arterial en ratas normotensas e hipertensas, debido probablemente a una disminución de la resistencia periférica total. El efecto hipotensor mayor observado en ratas hipertensas es causado probablemente por una vasodilatación potencializada, provocada por AFL.The aim of this study was to characterize the hypotensive response induced by the aqueous fraction of the ethanolic extract of the leaves (AFL) of Albizia inopinata in normotensive and chronically L-NAME-hypertensive rats. AFL induced dosedependent decreases in mean blood pressure (MAP) in both cases, however, hypotension was more pronounced in hypertensive rats. In isolated rat aortic rings, increasing concentrations of AFL were able to antagonize phenylephrine and KCl-induced contractions, however, IC 50 values for normotensive rats were significantly higher than that obtained for hypertensive rats. Furthermore, AFL-induced response was clearly endothelium-dependent since after removal of aortic endotelial cells and NO-synthase blockade, the relaxant response was significantly attenuated. The present work demonstrates that in normotensive and L-NAME-hypertensive rats, AFL lowers MAP, probably due to a decrease in peripheral resistances. The more pronounced hypotensive effect observed in hypertensive rats, is probably due to a strong vasodilation induced by AFL in these rats.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Comparison of the hypotensive effect induced by the ethanol extract of <i>Albizia inopinata</i> G. P. Lewis in normotensive and chronically L-NAME hypertensive rats

El objetivo del presente estudio fue caracterizar la respuesta hipotensora provocada por la fracción acuosa del extracto etanólico de hojas (AFL) de Albizia inopinata en ratas normotensas y hipertensas por el L-NAME (N-nitro-L-argininA metiléster). En las ratas normotensas, AFL provocó una disminución dosis-dependiente de la presión arterial, acompãnada de un aumento de la frecuencia cardíaca. Ya en el caso de las ratas hipertensas, AFL provocó una hipotensión más aguda, en tanto que las modificaciones de la frecuencia cardíaca no fueron significativas. En los anillos de la aorta, concentraciones crecientes de AFL antagonizaron las contracciones provocadas por fenilefrina y KCl; por otro lado, los valores de CI 50 para ratas normotensas fueron significantemente superiores a los obtenidos en ratas hipertensas. El efecto vasodilator de AFL parece ser claramente dependiente de la liberación de NO por el endotelio vascular. En conclusión, el presente estudio demuestra que AFL disminuye la presión arterial en ratas normotensas e hipertensas, debido probablemente a una disminución de la resistencia periférica total. El efecto hipotensor mayor observado en ratas hipertensas es causado probablemente por una vasodilatación potencializada, provocada por AFL.The aim of this study was to characterize the hypotensive response induced by the aqueous fraction of the ethanolic extract of the leaves (AFL) of Albizia inopinata in normotensive and chronically L-NAME-hypertensive rats. AFL induced dosedependent decreases in mean blood pressure (MAP) in both cases, however, hypotension was more pronounced in hypertensive rats. In isolated rat aortic rings, increasing concentrations of AFL were able to antagonize phenylephrine and KCl-induced contractions, however, IC 50 values for normotensive rats were significantly higher than that obtained for hypertensive rats. Furthermore, AFL-induced response was clearly endothelium-dependent since after removal of aortic endotelial cells and NO-synthase blockade, the relaxant response was significantly attenuated. The present work demonstrates that in normotensive and L-NAME-hypertensive rats, AFL lowers MAP, probably due to a decrease in peripheral resistances. The more pronounced hypotensive effect observed in hypertensive rats, is probably due to a strong vasodilation induced by AFL in these rats.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Natural products inhibitors of the angiotensin converting enzyme (ACE): a review between 1980 - 2000

Inhibition of Angiotensin Converting Enzyme (ACE) is a modern therapeutic target in the treatment of hypertension. Within the enzyme cascade of the renin-angiotensin system, ACE removes histidyl-leucine from angiotensin I to form the physiologically active octapeptide angiotensin II, one of the most potent known vasoconstrictors. Therefore, a rationale for treating hypertension would be to administer drugs or natural compounds which selectively inhibit ACE. The present work constitutes a review of the literature of plants and chemically defined molecules from natural sources with in vitro anti-hypertensive potential based on the inhibition of ACE. The review refers to 321 plants, the parts utilized, type of extract and whether they are active or not. It includes also the names of 158 compounds isolated from higher plants, marine sponges and algae, fungi and snake venom. Some aspects of recent research with natural products directed to produce anti-hypertensive drugs are discussed. In this review, 148 references were cited