Capacidad atrapadora de radicales libres, efectos citotóxicos y antiproliferativos de Vaccinium meridionale Sw. en líneas celulares de cáncer de colon

ABSTRACT: Vaccinium meridionale Swartz, of the family Ericaceae, is commonly known as mortiño or agraz. The plant is considered a functional food, with a content of anthocyanins and antioxidants similar to or greater than that reported for other Vaccinium species. However, little is known about its nutraceutical and medicinal properties. Objectives: determine the antioxidant activity and cytotoxic and antiproliferative effect of mortiño fruit aqueous extract against colon adenocarcinoma cells (SW480) and their derived metastatic cells (SW620). Methods: total phenols and anthocyanins were determined by the Folin-Ciocalteu method. Caffeoyl derivatives were determined by HPLC-DAD. Antioxidant activity was analyzed as the ability to scavenge reactive oxygen species (ROS), reactive nitrogen species (RNI), peroxyl radicals and hydroxyl radicals. Cytotoxic and antiproliferative activities were studied by MTT and sulforhodamine B. Results: the following substances were found in 100 g of lyophilized extract: total phenols (2 546 mg GAE), anthocyanins (150.7 mg C3G), chlorogenic acid (126 mg), ferulic acid (108 mg) and coumaric acid (63 mg). Hydroxyl radical scavenging capacity was 36 147.5 μmol DMSO, whereas ROS and RNS scavenging capacity was 29 255.9 y 41 775.2 μmolTrolox, respectively. ORAC value was 41 775.2 μmolTrolox. A dose-dependent cytotoxic and antiproliferative effect was observed. IC50 value was 59.12 μg/ml for SW480 and 56.10 μg/mL for SW620. Conclusions: mortiño fruit aqueous extract exhibited antioxidant, cytotoxic and antiproliferative activities comparable to those of other berries of the genus Vaccinium, which could be partly explained by the presence of a high content of anthocyanins and phenolic acids.RESUMEN: Vaccinium meridionale Swartz, pertenece a la familia Ericaceae, conocida comúnmente como mortiño agraz. Considerado un alimento funcional por su contenido de antocianinas y antioxidantes similares o mayor al reportado para otras especies de Vaccinium. Sin embargo, poco se conoce sobre sus propiedades nutracéuticas y en la salud. Objetivos: determinar en extracto acuoso del fruto mortiño, la actividad antioxidante y su efecto citotóxico y antiproliferativo en células de adenocarcinoma de colon (SW480) y sus derivadas metastásicas (SW620). Métodos: se determinó el contenido de fenoles y antocianinas totales por el método Folin-Ciocalteu, los derivados caffeoil por HPLC-DAD. La actividad antioxidante se analizó como habilidad para atrapar especies reactivas del oxígeno (ROS) y del nitrógeno (RNI), radicales peróxilo e hidróxilo. La actividad citotóxica y antiproliferativa se estudiaron por MTT y sulforodamina B. Resultados: en 100 g de liofilizado se encontrófenoles totales (2546 mg GAE), antocianinas (150,7 mg C3G), ácido clorogénico (126 mg), ácido ferúlico (108 mg) y cumárico (63 mg), capacidad atrapadora de radical hidroxilo fue 36147,5 μmol DMSO, capacidad atrapadorade ROS y RNS fue 29255,9 y 41775,2 μmol Trolox, respectivamente, valor ORAC 41775,2 μmol Trolox. Se observó un efecto citotóxico y antiproliferativo dosis-dependiente. El valor IC50 para SW480: 59,12 μg/mL y SW620: 56,10 μg/mL. Conclusiones: el extracto acuoso del fruto del mortiño exhibió actividades antioxidantes, citotóxicas y antiproliferativas comparables a las de otras bayas del género Vaccinium, lo que podría ser explicado parcialmente por la presencia del alto contenido de antocianinas y ácidos fenólicos

Efecto del consumo de un alimento con base de frutas y aditivos naturales en pacientes con riesgo cardiovascular

ABSTRACT: cardiovascular diseases (CVD), a group of disorders of the heart and blood vessels are the main cause of morbidity and mortality worldwide. Strategies for its prevention have been proposed, such as modifying life habits, including increasing the consumption of fruits and vegetables associated with the decrease in the probability of suffering CVD. Objective: to evaluate the effects of a base compote of guava (Psidium guajava) and passion fruit (Passiflora ligularis) on blood pressure and metabolic and inflammatory biomarkers in hypertensive type two diabetic patients. Methods: food characterization test (microbiological, proximal, sensorial, antioxidant activity and total phenols). The compote was administered for 21 days to 8 adults (30 to 65 years old); glycaemia, blood pressure, inflammatory markers, and BMI and waist circumference before and after the intervention were measured. Results: the sensory test showed: 66% acceptance and all attributes a value >3, indicating that it was well evaluated. The microbiological aspects comply with the safety for human consumption and nutritionally it stands out that the contribution of carbohydrates (12.3%) is adequate for these patients. The hydrophilic ORAC value was 98.570 μmol ET/g sample. In the patients at the end of the study, a statistically significant decrease in systolic blood pressure was observed (127 mmHg, p 0.041) and the pro-inflammatory markers TNFα, IL-1β and IL6 (31.9 pg/mL, p 0.012, 31.9 pg/mL, p 0.012, and 3.5 pg/mL, p 0.017 respectively) and glycaemia increase (157.5 mg/dL, p 0.036). Conclusions: the medium-term consumption of a compote based on guava, passion fruit, cinnamon and flaxseed oil improves systolic blood pressure and the pro- inflammatory markers TNFα, IL-1β and IL6 in diabetic and hypertensive patients.RESUMEN: : las enfermedades cardiovasculares (ECV), conjunto de trastornos del corazón y los vasos sanguíneos son la principal causa de morbilidad y mortalidad en todo el mundo. Se han propuesto estrategias para su prevención como modificar los hábitos de vida, incluyendo aumentar el consumo de frutas y verduras asociadas con la disminución en la probabilidad de sufrir ECV. Objetivo: evaluar los efectos de una compota base de guayaba (Psidium guajava) y granadilla (Passiflora ligularis) en la presión arterial y biomarcadores metabólicos e inflamatorios en pacientes diabéticos tipo 2 hipertensos. Métodos: caracterización del alimento prueba (análisis microbiológico, proximal, sensorial, actividad antioxidante y fenoles totales). Se suministró la compota durante 21 días a 8 adultos (30 a 65 años), se midió glicemia, presión arterial, marcadores inflamatorios, IMC y perímetro de cintura antes y después de la intervención. Resultados: la prueba sensorial mostró: 66% de aceptación, y todos los atributos un valor >3, indicando que fue bien evaluado. Los aspectos microbiológicos cumplen con la inocuidad para consumo humano y nutricionalmente se destaca que el aporte de carbohidratos (12,3%) es adecuado para estos pacientes. El valor ORAC hidrofílico fue 98,570 μmol ET/g muestra. En los pacientes al final del estudio se observó disminución estadísticamente significativa de la presión arterial sistólica (127 mm Hg; p 0,041) y los marcadores proinflamatorios TNFα, IL-1β e IL6 (31,9 pg/mL, p 0,012; 31,9 pg/mL, p 0,012; y 3,5 pg/ mL, p 0,017, respectivamente) e incremento de la glicemia (157,5 mg/dL, p 0,036). Conclusión: el consumo a mediano plazo de una compota a base de guayaba, granadilla, canela y aceite de linaza mejora la presión arterial sistólica y los marcadores pro inflamatorios TNFα, IL-1β e IL6 en pacientes diabéticos e hipertensos

Aqueous extract of golden berry (Physalis peruviana) : antiproliferative, apoptotic and antioxidant activities

ABSTRACT: Ethanolic extracts from P. peruviana showed cytotoxic activity against different cancer cell lines. Objective: To evaluate the antiproliferative activity of aqueous extract of the fruit golden berry in colon cancer cells. Materials and Methods: We analyzed cytotoxicity and selectivity index (SI) (MTT), antiproliferation (sulforhodamine-B), apoptosis (cell cycle, Annexin-V, receptors TRAIL-DR4/-DR5 and caspase-3), and antioxidant activity (content of total carotenoids and flavonoids). Results: The aqueous extract showed cytotoxic and antiproliferative effect on SW480 (IC50 = 44.2 µg/ml, SI = 11.6) and SW620 (IC50 = 85.1 µg/ml, SI = 6.0). The hypodiploid SW480 and SW620 cells increased 13% and 12% respectively as well as apoptotic SW480 and SW620 cells (19% and 21 %, respectively), expression of receptors TRAIL-DR4 /-DR5 (SW480: +59% / +53%; SW620: +67% / +65%) and activation of caspase-3. The aqueous extract scavenged OH- radicals, showed low oxygen radical capacity and low scavenging capacity for reactive oxygen and nitrogen species. The total flavonoids and carotenoids contente was 487.1 mg catechin y 0.9 mg β-carotene by 100 g powder, respectively. Conclusions: These findings suggest that golden berry may be a promising source of bioactive compounds with chemopreventive activity against human colon cancer.RESUMEN: Extractos etanólicos de P. peruviana han mostrado actividad citotóxica contra diferentes células cancerosas. Objetivo: estudiar la actividad anticancerígena de un extracto acuoso del fruto uchuva en células de cáncer de colon SW480 y SW620. Materiales y métodos: se analizaron citotoxicidad e índice de selectividad (SI) (MTT), antiproliferación (sulforodamina-B), apoptosis (ciclo celular, anexina-V, receptores TRAIL-DR4/-DR5 y caspasa-3), actividad antioxidante (contenido de flavonoides y carotenoides totales). Resultados: el extracto acuoso de uchuva mostró efecto citotóxico y antiproliferativo en células SW480 (IC50=44,2 µg/mL, SI=11,6) y SW620 (IC50=85,1µg/mL, SI=6,0). Las células hipodiploides SW480 y SW620 aumentaron 13% y 12%, respectivamente. Las células apoptóticas incrementaron 19% y 21% en SW480 y SW620, respectivamente, con incremento en la expresión de receptores TRAIL-DR4/-DR5 en SW480 (+59%/+53%) y SW620 (+67%/+65%), y activación de caspasa-3 en ambas líneas celulares. El extracto neutralizó radicales OH-, presentó baja capacidad reductora y atrapadora de especies reactivas del oxígeno y nitrógeno. El contenido de flavonoides y carotenoides fue 487,1 mg catequina y 0,9 mg β-caroteno por 100 g de liofilizado, respectivamente. Conclusiones: estos hallazgos sugieren que la uchuva puede ser una fuente prometedora de compuestos bioactivos con actividad quimiopreventiva en cáncer de colon humano

Antiproliferative and pro-apoptotic effects of Andean berry juice (Vaccinium meridionale Swartz) on human colon adenocarcinoma SW480 cells

ABSTRACT: Vaccium meridionale Swartz, commonly Andean Berry, has a high content of several phytochemicals, such as anthocyanins, phenolic acids, and other flavonoids. However, in spite of its antioxidant capacity, there is little information about its anticarcinogenic properties. This study evaluated the antiproliferative and pro-apoptotic activity of Andean Berry Juice (ABJ) on human colon adenocarcinoma SW480 cells. The antiproliferative activity of ABJ was evaluated on SW480 cells using the Sulphorodamine B assay.The effect on cell viability, cytotoxicity and activation of caspase-3 was analyzed using The ApoTox-GloTM Triplex Assay. Specific apoptotic biomarkers cleaved PARP, total Bcl-2-associated death promote (BAD), phosphorylated BAD, total p53, and phosphorylated p53 were also analyzed. To determine the intracellular redox-state, the Glutathione Assay Kit and 2′-7′- Dichlorodihydrofluorescein diacetate (DCFH-DA) were used, respectively. The antiproliferative assay showed a IC50 value of 8% v/v ABJ, the caspase 3 activity was increased in time-dependent manner in SW480 treated cells, the proapoptotic proteins (cleaved caspase 3, cleaved PARP, P53 and total BAD) were increased by 1.6 to 2.0 fold. In addition, the ABJ-treated SW480 cells increased significantly the production of intracellular reactive oxygen species (ROS), parallel with reduction in the intracellular content of glutathione (GSH) and consequently a decrease of GSH/ oxidized glutathione (GSSG) ratio. In conclusion, the ABJ was able to inhibit SW480 cells proliferation involving apoptotic mechanisms through the perturbation of intracellular oxidative state

Cytotoxic and apoptotic activities of the aqueous fruit extract of Passiflora edulis Sims var flavicarpa in an in vitro model of human colon cancer

ABSTRACT: Colorectal Cancer (CRC) is the fourth leading cause of cancer death in the world. Epidemiological studies have shown an association between CRC incidence/mortality with unhealthy dietary habits, which suggests the need to promote and protect health through the adoption of sustainable measures that allow the reduction of morbidity and mortality rates, such as the consumption of products of plant origin. Some phytochemicals derived from fruits have shown antiproliferative activity and high antioxidant capacity; however, few research advances have been obtained regarding the complex mixture of phytochemicals of certain fruits that could contain promising bioactive substances. For these reasons, in the present work we evaluated the cytotoxic activity and the pro-apoptotic potential of the aqueous extract of P. edulis Sims var. Flavicarpa on an in vitro CRC model. Chemical analysis of the extract was based on a preliminary phytochemical screening in which were identified metabolites such as phenolic compounds and sterols, which have displayed antitumoral properties. The extracts exerted cytotoxic and proapoptotic potential, demonstrated by the reduction on cell viability, increase of the SubG0/G1 cell populations and the positive staining with Annexin-V of treated cells. Our results suggest that P. edulis is a potential source of phytochemical compounds with cytotoxic and apoptotic potential over colon cancer cell lines

Mango (Mangifera indica cv. Azúcar) antiinflammatory and chemopreventive role during colorectal carcinogenesis

ABSTRACT: Chemopreventive activities of natural compounds result in the modulation of several pathways and molecular targets. It is common to find effective potential candidates for cancer chemoprevention with anti-inflammatory properties. Mango (Mangifera indica cv. Azúcar) has shown anticarcinogenic effects and it is a source of bioactive compounds. This study evaluated the effects of mango on Aberrant Crypt Foci formation and inflammatory biomarkers after initiation of colon carcinogenesis in AOM-treated mice. Ripped mango pulp (Mangifera indica cv. Azúcar) composition was identified by HPLC. Azoxymethane-treated mice received the fruit (0.3% w/v) for eight weeks and the distal part of colon was collected and stained with methylene blue to look for aberrant crypt foci (ACF); scrapped mucosal cells were processed for prostaglandin E2 detection by ELISA; and blood levels of pro-inflammatory cytokines (interleukin-1Beta, tumor necrosis factor-alpha, interleukin 6) were also assessed by ELISA. Student’s t.test was used for the comparisons between mango treated and untreated groups. ACF formation was reduced by 67.5% and prostaglandin E2 levels were also reduced in mice which ingested the fruit. Cytokines levels were unchanged by mango consumption. In the chromatography were identified phenolic acids and Beta-carotene. Mango pulp showed chemopreventive effects through the reduction of ACF formation, by means of blocking hyperproliferation which is correlated with decreasing levels of PGE2

Vitamin D and Healthy Bone

ABSTRACT: Vitamin D plays an essential role in calcium homeostasis and bone health, however researches during last years have elucidated other biological actions of its active form 1,25-Dihydroxyvitamin D (1,25 (OH2) D3 (D2)) on target cells. This vitamin is considered as a hormone too, because it is produced and metabolized to the active form that is able to induce through its nuclear receptor, target gene transcription, which are responsibles for maintenance of serum calcium at the physiological level and the bone health. Finally, this review proposes that consuming a balanced diet along with the suitable sunlight exposure, it coul be a preventive strategy to decrease risk of bone pathologies and to maintain normal physiological level of vitamin D. In humans vit D can be affected by nutritional, environmental, physiological and cultural factors.RESUMEN: La vitamina D tiene un papel esencial en la homeostasis del calcio y de la salud ósea, sin embargo, investigaciones recientes han revelado que su forma activa, la 1,25 Dihidroxivitamina D (1,25 (OH2) D3 (D2)) tiene otras acciones biológicas en las células blanco. Esta vitamina es también considerada como una hormona, porque es producida y metabolizada a la forma activa, capaz de inducir a través de su receptor nuclear la transcripción de genes blanco responsables del mantenimiento del calcio sérico, a nivel fisiológico, y de la salud ósea. Finalmente, esta revisión propone que una alimentación balanceada junto con la adecuada exposición a la luz solar es una estrategia preventiva para disminuir el riesgo de patologías óseas y mantener el rango fisiológico normal de vitamina D en humanos, el cual es afectado por factores nutricionales, ambientales, fisiológicos y culturales

Cytotoxic effect and antioxidant activity of Andean berry (Vaccinium meridionale Sw) wine

ABSTRACT: Vaccinium meridonale Sw or Andean berry has antioxidant properties due to its high content of polyphenols, as anthocyanins and phenolic acids. Polyphenols have been associated with the prevention of chronic and cardiovascular diseases. In the last years, alcoholic drinks have been studied for their composition and health benefits. By this, the aim of this research was to obtain three types of alcoholic beverages from Andean berry, which have different treatments. The methods used to obtain the beverages were macerated fruit machine (MAC), preheating of the fruit (CAL) and by combining both of them (MIX). The antioxidant activity was evaluated by FRAP, DPPH, ORAC methods and anthocyanins and total phenols were measured. Finally, the antiproliferative effect was evaluated on a colon cancer cell line (SW480). Findings suggest that ethanol content of final products is not altered by treatment of unfermented Andean berry juice (must). The alcohol concentrations for MAC, CAL and MIX drinks were 90±1.7, 89±3.6 and 94±4.1 g/L, respectively. The results showed that CAL and MIX methods favor the extraction of secondary metabolites and consequently increase the antioxidant activity. The fermentation process affected the antioxidant power and total phenolic content in beverages CAL and MIX. However, no significant changes in these parameters were observed in the MAC drink. These beverages can eventually reduce the cancer cell viability between 15.1 (20 μg/L) and 37.2% (200 μg/mL). Thus, it was concluded that MIX treatment has higher antioxidant power and it could reduce the cancer cell viability

Activación diferencial de la apoptosis vía Fas (CD95) por procianidinas de manzana en células humanas de cáncer de colon y sus derivadas metastásicas

Introduction: We investigated the effects of apple procyanidins (Pcy), oligomers of catechins and epicatechins on Fas receptor expression and function in human colon adenocarcinoma cells (SW480) and in their derived metastatic cells (SW620). Methods: Pcy were characterized by reverse-phase HPLC. Cell death, Fas proteins, DNA fragmentation, and mitochondrial membrane potential were analyzed by flow cytometry. Fas mRNA was analyzed by RT-PCR in real time. Results: Pcy up-regulated the expression of the Fas receptor at the cell surface of both cell lines but activated Fas gene transcription only in SW620 cells. In SW480 cells, Pcy combined with Fas agonist CH-11 enhanced Fas-mediated apoptosis involving the loss of mitochondrial membrane potential and DNA fragmentation, which were abrogated by the antagonist antibody of Fas receptor, the anti-Fas ZB4. On the contrary, in SW620 cells, CH-11 was not able to enhance Pcy-triggered apoptosis indicating that Fas receptor-mediated apoptosis was not activated in these cells despite an up-regulation of Fas receptor gene expression. However, it was observed in SW620 cells that Pcy activated the Fas receptor-mediated apoptotic pathway after a specific blockage of TRAIL-death DR4/DR5 receptors. Conclusions: The present data showed that Pcy were able to activate the Fas receptor apoptotic pathway in SW480 cells and favored a cross-talk between TRAIL and Fas receptors in SW620 cells because specific blocking of TRAIL death receptors favored activation of the Fas receptor-mediated apoptosis. These important data may allow the emergence of new therapeutic protocols targeting death receptors against resistant metastatic cells. Introducción: Se estudiaron los efectos de procianidinas (Pcy) de manzana, oligómeros de catequinas y epicatequinas en la expresión y función del receptor Fas en células humanas de cáncer de colon (SW480) y sus derivadas metastásicas (SW620). Métodos: Las Pcy se caracterizaron por cromatografía líquida de alta presión (HPLC) en fase-reversa. Se analizaron por citometría de flujo la muerte celular, la proteína Fas, la fragmentación del ADN y el potencial de la membrana mitocondrial. Se analizaron los transcriptos de Fas por RT-PCR en tiempo real.Resultados: Las Pcy aumentaron la expresión del receptor Fas en la superficie celular de ambas líneas celulares pero la transcripción del gen Fas fue activado transcripcionalmente sólo en las células SW620. En las células SW480, las Pcy combinadas con el agonista de Fas CH-11 potenció la apoptosis mediada por Fas involucrando la pérdida del potencial mitocondrial de membrana y la fragmentación del ADN los cuales fueron evadidos por el anticuerpo antagonista del receptor Fas anti-ZB4. Por el contrario, en las células SW620, CH-11 no fue capaz de potenciar la apoptosis activada por Pcy indicando que la apoptosis mediada por el receptor Fas no fue activada en estas células a pesar del aumento en la expresión de Fas por regulación a nivel transcripcional. Sin embargo, se observó en las células SW620 que las Pcy activaron la vía apoptótica mediada por el receptor Fas después de un bloqueo específico de los receptores de muerte TRAIL DR4/DR5. Conclusiones: Estos datos muestran que las Pcy fueron capaces de activar la apoptosis a través del receptor Fas en las células SW480 y favorecieron una intercomunicación entre los receptores TRAIL y Fas en las células SW620 debido a que el bloqueo específico de los receptores de muerte TRAIL favoreció la activación de la apoptosis mediada por el receptor Fas. Estos datos podrían permitir el surgimiento de nuevos protocolos terapéuticos dirigidos contra receptores de muerte en células metastásicas resistentes

Impact of Colombian yellow fruits and tropical fruits drinks consumption on the antioxidant status of healthy women

ABSTRACT: Reactive oxygen species are responsible for causing different types of damage in the body which are associated with the onset of chronic non-communicable diseases. A strategy to counteract these effects is by a diet rich in antioxidants compounds found in fruits. The aim of this study was to determine the antioxidant capacity in plasma and the content of total phenolic compounds in healthy women who consumed a drink prepared with Nativanox® Colombian tropical fruits or a drink prepared with Nativanox® Colombian yellow fruits during a short period of time. Nineteen healthy women received a daily 200 mL drink with Nativanox® Colombian tropical fruits or a drink with Nativanox® Colombian yellow fruits for 14 days. Before and after the intervention period blood and plasma were obtained to analyze C-reactive protein levels, lipid profile, total phenolic content and antioxidant status through FRAP, ABTS and EROS methods. Regular consumption of a drink with Nativanox® Colombian tropical fruits had a positive impact on the lipid profile and the antioxidant capacity on plasma of healthy women. The consumption of a drink with Nativanox® Colombian yellow fruits diminished diastolic blood pressure. These results showed that a Nativanox® Colombian yellow and tropical fruit contains bioactive compounds that can improve oxidative status in plasma and contribute to reduce the risk of cardiovascular disease