Caracterización farmacológica de los compuestos derivados del ácido cinámico de la raíz de Sechium edule (Jacq.) Sw. y su efecto sobre la disfunción endotelial

Systemic hypertension is a multifactorial condition that is closely associated with metabolic syndrome in conjunction with diabetes mellitus type 2 and dyslipidemia related to obesity. Each of these pathophysiologies independently cause endothelial dysfunction, so that in the diabetic patients that generate endothelial dysfunction will lead to cardiovascular problems, mainly hypertension, likewise hypertensive patients can generate diabetes mellitus type 2. The endothelium is a protective barrier and modulator that covers the entire cardiovascular system in order to maintain body homeostasis, endothelial cells control blood pressure, regulating vascular tone and permeability, coagulationfibrinolysis balance, cell adhesion, leading to the leukocyte diapedesis thereby establishing an inflammatory process, under normal conditions. When this tissue is compromised by disorders such as hypertension, diabetes or dyslipidemia its functions are altered leading to endothelial dysfunction, which in turn promotes the metabolic syndrome disorders. Medications today are for treating hypertension, usually act on a single mechanism of action, resulting in a polypharmacy, which generally do not reverse or prevent endothelial dysfunction conclusively. Therefore, it is significantly greater to control the degenerative effects of the diseases, reducing the alterations and damage caused by endothelial dysfunction. Because of this, the search for treatments derived from natural products is an alternative in the control of these diseases due to the richness in active compounds that can act synergistically through different mechanisms of action. The species S. edule also known as Chayote, is a plant native to Mexico, which has been used in traditional medicine to treat vascular and renal disorders. Also chemical and pharmacological studies have been done, and are classified as a vasodilating agent containing polyphenolic compounds, which are known to have different activities like oxidative stress, inflammation, and hypertension, among others. The effect of the root extracts of S. edule was evaluated on a model of endothelial dysfunction caused by hypertension induced with angiotensin II (AGII), in which the levels of oxidative stress and the pro-inflammatory state were analysed, as well as the vasorelaxing ability that was performed on the isolated rat aorta ring model, which also could approach a possible model of action for these extracts. The results indicate that the extract SeAce reduced systolic blood pressure by 26% and diastolic by 28%, while the extract SeMeOH reduction them in order of 27% to 28% for systolic and diastolic respectively, compared to the damage group that was administered angiotensin II for 10 weeks at a sub-effective dose. In the oxidative stress study samples of brain, kidney and aorta were analysed for O2 !― anion production thru a dihydroethidium fluorometry test in which it was possible to establish that extracts of S. edule statistically significant reduced O2 !― anion levels in brain, kidneys and aorta compared to the levels shown by the negative control group (angiotensin II) and for the group treated with Losartan except in the aorta results, which presented the lowest levels of O2 !― anion, however Losartan almost doubled these levels in brain above angiotensin II group, this can be due to the products of the biotransformation of Losartan in the brain, these being able to increase the production of O2 !― anion. For cytokine levels, SeMeOH extract causes a decrease in the concentration of TNF-α by 31%, IL-1β by 9%, IL-6 in 23% and IL-10 in 18%, relative to the increase obtained in the angiotensin II group. Furthermore, in the histological analysis of the kidney from animals with and without angiotensin II treatment and with S. edule extracts, it was observed that mice that received only angiotensin II presented evident damaged of the organ with changes of the tissue structure. This damage caused by angiotensin II was attenuated with treatments derived from the S. edule extracts. Testing of isolated rat aorta contributed to propose that this plant is able to exert vasorelaxant effect of vascular smooth muscle following by the administration of vasoconstrictor angiotensin II. The information is this work showed that extracts of S. edule are able to antagonize the effects of angiotensin II, probably by acting on AT1 receptors for this hormone, which is due to the presence of polyphenolic compounds primarily cinnamic acid derivatives that are present in the extracts evaluated.La hipertensión arterial sistémica es un padecimiento multifactorial que se asocia de manera estrecha con el síndrome metabólico en conjunto con la diabetes mellitus tipo 2 y la dislipidemia relacionadas a la obesidad. Cada una de estas fisiopatologías de manera independiente provocan disfunción endotelial, por lo que en el paciente diabético se genera disfunción endotelial que a su vez conduce a problemas cardiovasculares, principalmente la hipertensión arterial sistémica, de igual manera el paciente hipertenso puede llegar a generar diabetes mellitus tipo 2. El endotelio es una barrera protectora y moduladora que recubre a todo el sistema cardiovascular para mantener la homeostasis corporal, las células endoteliales controlan la presión arterial, regulan el tono y la permeabilidad vascular, el balance coagulación-fibrinólisis, la adhesión celular que conduce a la diapédesis de leucocitos estableciendo con ello el proceso inflamatorio, todo esto en condiciones de normalidad. Cuando este tejido se ve comprometido por alteraciones como la hipertensión, diabetes o dislipidemia se alteran sus funciones conllevando a la disfunción endotelial, que a su vez promueve o establece la conjunción del síndrome metabólico. Los medicamentos actuales para tratar la hipertensión arterial sistémica, por lo general actúan sobre un sólo mecanismo de acción, lo que deriva en una polifarmacia que generalmente no revierten o impiden la concluyente disfunción endotelial. Por lo tanto, es de gran importancia poder controlar no sólo a las enfermedades crónico degenerativas, sino también, poder disminuir las alteraciones y daños provocados por la disfunción endotelial. Debido a esto, la búsqueda de tratamientos derivados de productos naturales es una alternativa en el control de estos padecimientos ya que su riqueza en compuestos activos puede actuar de manera sinérgica mediante diferentes mecanismos de acción. La especie Sechium edule también conocida como Chayote, es una planta originaria de México, que ha sido empleada en la medicina tradicional para tratar afecciones vasculares y renales. Así mismo, en estudios farmacológicos y químicos se ha podido catalogar como un agente vasodilatador que contiene compuestos de tipo polifenólicos, los cuales se sabe tienen actividades diversas sobre el estrés oxidante, la inflamación y la hipertensión arterial, entre otros. Por lo que en este trabajo se realizó un estudio del efecto de los extractos de raíz de Sechium edule en un modelo de disfunción endotelial provocado por hipertensión arterial sistémica inducida con angiotensina II en el cual se investigaron los niveles de estrés oxidante, así como el estado proinflamatorio, la capacidad vasorrelajante en anillos aislados de rata donde, además se pudo aproximar a un posible modo de acción de estos extractos. Los resultados indican que el extracto SeAce redujo la presión arterial sistólica en un 26% y la diastólica en un 28 %, mientras que el extracto SeMeOH induce una reducción de un 27% para sistólica y 28% para la diastólica, con respecto al grupo con daño inducido por la administración por 10 semanas y a una dosis sub-efectiva de angiotensina II. En el ensayo de estrés oxidante se analizó en muestras de cerebro, riñón y aorta la producción de anión O2 !― por medio de una prueba de fluorometría con dihidroetidio en el cual se logró establecer que los extractos de S. edule logran reducir de manera estadísticamente significativa los niveles de anión O2 !— en cerebro, riñones y aorta respecto a los niveles presentados por el grupo control negativo de angiotensina II, así como para el grupo tratado con Losartán exceptuando en los resultados de aorta, la cual presento los niveles más bajos de anión O2 !—, sin embargo en cerebro Losartán casi duplicó estos niveles por encima del grupo angiotensina II, esto puede estar dado por los productos derivados de la biotransformación a nivel cerebral del Losartán, siendo estos capaces de aumentar la producción del O2 !—. En el caso de los niveles de citocinas, el extracto SeMeOH provoca una disminución en la concentración de TNF-α en un 31%, de IL-1β en un 9%, de IL-6 en un 23% y de IL-10 en un 18%, con respecto al incremento obtenido en el grupo angiotensina II. Por otro lado, en el análisis histológico de riñones aislados de animales con y sin tratamiento con extractos de Sechium edule, se pudo observar que los ratones que recibieron sólo angiotensina II, presentan un órgano dañado, con cambios tisulares evidentes. Este daño ocasionado por la angiotensina II, fue atenuado con el tratamiento derivado de Sechium edule. El ensayo de aorta aislada de rata contribuyó a proponer que esta planta es capaz de ejercer un efecto vasorelajante de músculo liso vascular, tras la administración del vasoconstrictor angiotensina II. La información que este trabajo arrojó es que los extractos de Sechium edule son capaces de antagonizar los efectos de AGII, probablemente por actuar sobre los receptores AT1 para esta hormona, lo cual se debe a la presencia de compuestos polifenólicos en los extractos evaluados, principalmente derivados del ácido cinámico

Extracts and Fractions from Edible Roots of Sechium edule

Sechium edule is traditionally used in Mexico as a therapeutic resource against renal diseases and to control high blood pressure. The purpose of this work is to evaluate the antihypertensive effect of the hydroalcoholic extract obtained from the roots of this plant, including its fractions and subfractions, on different hypertension models induced with angiotensin II (AG II). The hydroalcoholic extract was tested on an in vitro study of isolated aorta rings denuded of endothelial cells, using AG II as the agonist; this assay proved the vasorelaxant effect of this extract. Vagotomized rats were administered different doses of AG II as well as the Hydroalcoholic extract, which reduced blood pressure in 30 mmHg approximately; subsequently this extract was separated into two fractions (acetone and methanol) which were evaluated in the acute hypertension mouse model induced with AG II, where the acetone fraction was identified as the most effective one and was subsequently subfractioned using an open chromatographic column packed with silica gel. The subfractions were also evaluated in the acute hypertension model. Finally, the extract, fraction, and active subfraction were analyzed by MS-PDA-HPLC, identifying cinnamic derivative compounds like cinnamic acid methyl ester

Pharmacokinetic Study of Biotransformation Products from an Anxiolytic Fraction of Tilia americana

An anxiolytic fraction of Tilia americana standardized in tiliroside, rutin, quercitrin, quercetin glucoside, and kaempferol was obtained. After oral administration of the fraction, the above-mentioned flavonoids were not detected in plasma over 24 h. However, meta and para hydroxyphenylacetic acid and dihydroxyphenylacetic acid (m-HPAA, p-HPAA and DOPAC) were monitored. These are the biotransformation compounds of the aglycones of kaempferol and quercetin; these aglycones are products of the other flavonoids present in the anxiolytic fraction. The analytical methods (HPLC) for flavonoids and the related compounds (m-HPAA, p-HPAA and DOPAC) were validated, determining the parameters of accuracy, precision, specificity or selectivity, limit of detection, quantification range, and robustness. The pharmacokinetic assay was performed with ICR mice strains, which were given 200 mg/kg of the standardized active fraction. The results of validation of the analytical methods were obtained, allowing it to be established in a validated way that no flavonoids present in the anxiolytic fraction of T. americana were detected in plasma. However, detection and follow up was possible for the serum levels of m-HPAA, p-HPAA, and DOPAC. The three compounds follow a two-compartment model with very similar parameters between m-HPAA and p-HPAA, some being different from the ones characterized in the pharmacokinetics of DOPAC

Data of the effects of acetone fraction from Sechium edule (Jacq.) S.w. edible roots in the kidney of endothelial dysfunction induced mice

Endothelial dysfunction induced by Angiotensin II (AG II) plays an important role in the pathogenesis of hypertension and is accompanied by a prooxidative condition, which in turn induces an inflammatory state, vascular remodeling, and tissue damage including the kidney (Schmitt and Dirsch, 2009) [1]. New drugs that can control several of these pathologies are required. Sechium edule has been reported to possess antioxidant, anti-inflammatory and antihypertensive activity (Ibarra-Alvarado et al., 2010) [2]. This paper contains data complementary to those published in Journal of Ethnopharmacology (Moreno et al., 2018) [3], evaluating the effect in kidney of hypertensive mice of the acetone fraction from S. edule to control de pro-oxidative state, reduction of the inflammatory adhesion molecule (ICAM) and recruitment of inflammatory cells