Modelo de aorta aislada y su contribución a la Fitofarmacología

Desde principios de los años 50 hasta ahora la aorta torácica aislada ha sido un modelo tradicional y productivo para estudios farmacológicos. Este modelo experimental ha estado estrechamente relacionado con la investigación realizada por el Dr. Robert Furchgott. El descubrimiento de la función del endotelio en la vasodilatación inducida por la acetilcolina (ACh), representó un hito en las ciencias biológicas y también tuvo una consecuencia importante en la preparación de aorta aislada. En este trabajo se describe la técnica de aorta aislada y las mejoras realizadas en el laboratorio del Dr. Penna en la Facultad de Medina, Universidad de Chile, así como la contribución de investigadores mexicanos. Puesto que el endotelio juega un papel clave en la relajación vascular y su disfunción es uno de los primeros indicadores (biomarcadores) de enfermedad cardiovascular, el modelo de aorta aislada es una valiosa preparación. Teniendo en cuenta la gran cantidad de fitoquímicos presentes en muchas fuentes naturales como verduras, frutas y plantas medicinales, podemos esperar que este modelo continúe entregando importantes aportes al conocimiento en farmacología y fitofarmacología

Ácido p-cumárico reduce el deterioro mediado por alta glucosa de la relajación dependiente de endotelio en aorta de rata

El ácido p-cumárico (p-CA) es un metabolito ubicuo en plantas, con propiedades antioxidantes, anti-inflamatoria, y anticancerígenas. El presente estudio fue diseñado para evaluar los efectos preventivos de p-CA sobre la relajación dependiente de  endotelio, deteriorada por niveles altos de glucosa (HG) (D-glucosa 25 mM) en aorta torácica aislada de rata. Los anillos aórticos obtenidos  de ratas macho Sprague-Dawley se montaron en un baño de órganos y fueron pre-tratados durante 3 h con D-glucosa 5 mM, HG, y HG más  de p-CA (1, 10 y 100 μM). Después de este período de tiempo se evaluó la relajación dependiente de endotelio mediante la adición  acumulativa de acetilcolina (ACh) en anillos pre-contraídos con fenilefrina (PE) (0,1 μM). p-CA mostró un moderado efecto vasodilatador  dependiente de endotelio (Emax = 29,28  1,89%, N = 6; pD2 = 6,075  0,184, N = 6). Cuando los anillos aórticos se pre-incubaron durante  3 h con HG, la Emax para ACh se redujo drásticamente desde 87,69  2,59% (N = 6) a 40,54  1,78% (N = 6). El efecto negativo de HG se  revirtió parcialmente, de manera dependiente de concentración, en los anillos co-incubados con p-CA tal como lo muestra el valor de Emax  para cada concentración de p-CA: 1 μ M (48,57  1,82%), 10 μM (60,81  1,80%) y 100 μM (64,51  1,80%). La acción de p-CA se asoció  con un cambio significativo en la Emax. No se observó diferencia estadísticamente significativa en el pD2. Nuestros resultados muestran  claramente que p-CA protege la relajación dependiente de endotelio inducida por ACh, la cual es afectada por HG en anillos aislados de  aorta de rata

Centaurium cachanlahuen (Mol.) Robinson una planta nativa chilena con efecto vasodilatador

Centaurium cachanlahuen (Mol.) Robinson es una planta nativa chilena ampliamente utilizada en medicina tradicional para el tratamiento de varias enfermedades, que incluyen alteraciones cardiovasculares. Estudios llevados a cabo en ratas normales e hipertensas sugieren que el extracto de Centaurium cachanlahuen tiene efecto antihipertensivo. El propósito de este trabajo fue evaluar el efecto de extractos acuosos e hidroalcohólicos de Centaurium cachanlahuen sobre la reactividad vascular de aorta de rata precontraída con fenilefrina (0.1 μM). Tanto el extracto acuoso (3 mg/mL) como el extracto hidroalcohólico (3 mg/mL) produjeron relajación de aorta de rata, la cual fue de mayor magnitud (P < 0.001) con el extracto hidroalcohólico respecto del extracto acuoso. El efecto observado tuvo un importante componente mediado por óxido nítrico (NO), tal como lo demuestra la inhibición de esta respuesta en presencia de N-nitro-L-arginina (L-NNA, 100 μM), un inhibidor de la óxido nítrico sintasa (NOS). Se sugiere que las xantonas presente en la planta pueden jugar un papel clave en el efecto vasodilatador observado por los extractos de Centaurium cachanlahuen. Este estudio constituye una evidencia experimental que apoya el uso popular de Centaurium cachanlahuen como agente hipotensor

Vasodilatory properties of Solanum crispum Ruiz & Pav. a South American native plant

Solanum crispum Ruiz & Pav. (S. crispum) is a southern South American native plant that is usually used in traditional medicine for the treatment of symptoms associated with both, acute and chronic ailments. Enema and infusion of leaves and stems are used to treat fever, headache, inflammation and hypertension. In this study, we aim to assess the vasoactive effect of hydroalcoholic extracts of S. crispum on isolated rat aorta rings. The hydroalcoholic extract of S. crispum induced a vasodilatory effect (42.6 ± 4.1%) in aortic rings precontracted with phenylephrine (0.1 μM). The aortic relaxation was largely endothelium-dependent and mediated by nitric oxide (NO). The endothelium- and NO-dependence was demonstrated by a drastic fall in the dilatation induced by the extract when the endothelium was removed (10.6 ± 2.3%) and when nitric oxide synthase (NOS) was inhibited (12.3 ± 2.5%) by nitro-L-arginine (L-NNA). This result supports the popular use of S. crispum in the treatment of hypertension that may be due, at least in part, to the vasodilator effect of one o more compounds present in their leaves and stems. Further studies should be performed to clarify this phenomenon

A Review of the Actions of Endogenous and Exogenous Vasoactive Substances during the Estrous Cycle and Pregnancy in Rats

Vascular endothelium plays a key role in regulating cardiovascular homeostasis by controlling the vascular tone. Variations in sex hormones during the reproductive cycle of females affect the homeostasis of the cardiovascular system. Also, the evidence shows that estrogens show a cardioprotective effect. On this basis, this study describes some vascular responses induced by vasoactive substances during the estrous cycle in rats. We obtained the information available on this topic from the online databases that included scientific articles published in the Web of Science, PubMed, and Scielo. Many investigations have evaluated the vasoactive response of substances such as acetylcholine and norepinephrine during the estrous cycle. In this review, we specifically described the vascular response to vasoactive substances in rats during the estrous cycle, pregnancy, and in ovariectomized rats. In addition, we discussed the existence of different signaling pathways that modulate vascular function. The knowledge of these effects is relevant for the optimization and development of new treatments for some vascular pathologies

The pulmonate limpet Siphonaria lessoni: Pharmacological study of norsiphonarienone, a polipropionate

We presented a marine natural product, norsiphonarienone, isolated from Siphonaria lessoni, a pulmonate limpet of Central Chile. The norsiphonarienone was pharmacologically studied in rat thoracic aorta with endothelium previously contracted with phenylephrine. This technique has been widely used to describe pharmacological characterization and seek for mechanisms of action of natural products and other physiological phenomena. The main characteristics described are pD2 (-log EC50) and maximum effect or maximal contraction (Emax). The results show that norsiphonarienone induced a significant difference in the maximal contraction and also in the pD2 (-log EC50)

Effects of two bisbenzylisoquinoline alkaloids, Antioquine and Tetrandrine, compared to Verapamil in Rat Thoracic Aorta

ABSTRACT The objective of this study was to compare two alkaloids (antioquine and tetrandrine) with verapamil; knowing that the smooth muscle respond to KCl and relationships with calcium. The effects of antioquine and tetrandrine, was studied in adults Wistar rat with modified methods used in the determination of aorta contractility and compared with verapamil effect in the same assays. The analysis of the effect of a drug or extract on aortic reactivity included maximal relaxation or maximal contraction (Cmax) (Phase 1). In our results, verapamil induced a blockade of 98.7 ± 0.7% (n = 6) in presence of endothelium and 97.9 ± 4.3% in ausence of endothelium, both in phase 1 and in phase 2 of 47.4 ± 4.1% (n = 6) in aortas in the presence of endothelium and 61.8 ± 1.1% in ausence of endothelium; Tetrandrine assays showed a phase 1 blocking effect of 63.4 ± 5.5 and 47.7 ± 2.9% (with and without endothelium, respectively) and phase 2 of 43.5 ± 6.2 and 28.5 ± 5.7%, (with and without endothelium, respectively). Antioquine presents in phase 1 and phase 2, a blockade that is not significant from the point of view of calcium antagonism. We can conclude that tetrandrine block the movement of calcium from both intracellular and extracellular deposits, with the greatest effect when aortas are in the presence of endothelium

New 1H-Benzo[f]indazole-4,9-diones Conjugated with C-Protected Amino Acids and Other Derivatives: Synthesis and in Vitro Antiproliferative Evaluation

1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, l-alanine, l-phenylalanine and l-glutamic acid) 6a–l were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f]indazole-4,9-dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation reactions. The chemical structures of the synthesized compounds were elucidated by analyzing their IR, 1H-NMR and 13C-NMR spectral data together with elemental analysis for carbon, hydrogen and nitrogen. The preliminary in vitro antiproliferative activity of the synthesized derivatives was evaluated on KATO-III and MCF-7 cell lines using a cell proliferation assay. The majority of the derivatives exhibited significant antiproliferative activity with IC50 values ranging from 25.5 to 432.5 μM. These results suggest that 1H-benzo[f]indazole-4,9-dione derivatives are promising molecules to be researched for developing new anticancer agents

Characterization of Fruit Development, Antioxidant Capacity, and Potential Vasoprotective Action of Peumo (<i>Cryptocarya alba</i>), a Native Fruit of Chile

The peumo (Cryptocarya alba) is a native fruit from central Chile that belongs to the Lauraceae family. To characterize the development and the potential health benefits of this edible fruit, quality and physiological parameters, along with antioxidant capacity, were evaluated during three clearly defined developmental stages of the fruit in two seasons. The most distinguishable attributes of ripe fruit were the change in size and color. Low CO2 production and no detectable ethylene levels suggested non-climacteric behavior of the peumo fruit. Peumo demonstrate a significant increase in their antioxidant capacity per 1 g of fresh weight (FW) of the sample, from small to ripe fruit. Higher values in ripe fruit (FRAP: 37.1–38.3 µmol FeSO4/gFW, TEAC: 7.9–8.1 mmol TE/gFW, DPPH: 8.4-8.7 IC50 μg/mL, and ORAC: = 0.19–0.20 mmol TE/gFW) were observed than those in blueberry fruit (FRAP: 4.95 µmol FeSO4/gFW, TEAC: 1.25 mmol TE/gFW, DPPH: 11.3 IC50 μg/mL, and ORAC: 0.032 mmol TE/ gFW). The methanol extracts of ripe fruit displayed the presence of polyphenol acids and quercetin, an ORAC value of 0.637 ± 0.061 mmol TE per g dried weight (DW), and a high cellular antioxidant and anti-inflammatory potential, the latter exceeding the effect of quercetin and indomethacin used as standard molecules. Also, the assay of isolated rat aorta with endothelium-dependent relaxation damage demonstrated that the peumo extract induced vascular protection, depending on its concentration under a high glucose condition. These results demonstrate that these endemic fruits have a good chance as ingredients or foods with functional properties