ES2397175B1 - Phenolic compounds of olive oil in a given concentration and its uses - Google Patents
Phenolic compounds of olive oil in a given concentration and its uses Download PDFInfo
- Publication number
- ES2397175B1 ES2397175B1 ES201131058A ES201131058A ES2397175B1 ES 2397175 B1 ES2397175 B1 ES 2397175B1 ES 201131058 A ES201131058 A ES 201131058A ES 201131058 A ES201131058 A ES 201131058A ES 2397175 B1 ES2397175 B1 ES 2397175B1
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- phenolic compounds
- olive oil
- oil
- food
- application
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Abstract
Compuestos fenólicos del aceite de oliva en una determinada concentración y sus usos.#Uso de compuestos fenólicos del aceite de oliva en una determinada concentración, para la elaboración de un medicamento o composición farmacéutica o alimentaria, para la prevención o el tratamiento de la arteriosclerosis en humanos.Phenolic compounds of olive oil in a certain concentration and their uses. # Use of phenolic compounds of olive oil in a certain concentration, for the preparation of a drug or pharmaceutical or food composition, for the prevention or treatment of arteriosclerosis in humans.
Description
Compuestos fenólicos del aceite de oliva en una determinada concentración y sus usos Phenolic compounds of olive oil in a given concentration and its uses
La presente invención se encuentra dentro del campo de la nutrición, la medicina y la farmacología, y se refiere al uso de compuestos fenólicos del aceite de oliva en una determinada concentración, para la elaboración de un medicamento The present invention is within the field of nutrition, medicine and pharmacology, and refers to the use of phenolic compounds of olive oil in a certain concentration, for the preparation of a medicament
o composición farmacéutica o alimentaria, para la prevención o el tratamiento de la arteriosclerosis en humanos. or pharmaceutical or food composition, for the prevention or treatment of arteriosclerosis in humans.
Uno de los métodos de cocina más usuales para preparar comida es la fritura. Este proceso puede afectar significativamente la cantidad y calidad de la ingesta de grasas, afectando a la salud del consumidor. Durante la fritura, la grasa sufre importantes cambios en su composición. En la fritura profunda, se producen reacciones químicas, como son los procesos de hidrólisis y oxidación, que afectan tanto a las cualidades nutricionales y sensoriales del alimento consumido como a la seguridad del consumidor. Además, el calentamiento del aceite reduce el contenido natural de los antioxidantes y genera compuestos tóxicos tales como polímeros y compuestos polares. En la generación de estos compuestos tóxicos, durante el proceso de calentamiento, influyen características intrínsecas del aceite, como el grado de insaturación de su contenido graso o su riqueza en agentes antioxidantes, y factores relacionados con la técnica del calentamiento, como la duración, temperatura y número de calentamientos. Los aceites de semillas tienen menor contenido de antioxidantes que el aceite de oliva, en especial que el aceite de oliva virgen y extravirgen, haciéndolo más vulnerables al calentamiento y generando tras su ingesta un incremento en la oxidación de lipoproteínas. Algunas opciones para mejorar la estabilidad de los aceites fritos incluyen la composición modificada en ácidos grasos, como el de girasol alto y medio oleico o el de canola alto oleico y bajo linolénico. Sin embargo, los aditivos son una alternativa potencial para prevenir la oxidación del aceite de fritura, siendo capaz de mejorar su rendimiento. One of the most common cooking methods for preparing food is frying. This process can significantly affect the quantity and quality of fat intake, affecting the health of the consumer. During the frying, the fat undergoes important changes in its composition. In deep frying, chemical reactions occur, such as hydrolysis and oxidation processes, which affect both the nutritional and sensory qualities of the food consumed and the safety of the consumer. In addition, heating the oil reduces the natural content of antioxidants and generates toxic compounds such as polymers and polar compounds. In the generation of these toxic compounds, during the heating process, intrinsic characteristics of the oil influence, such as the degree of unsaturation of its fat content or its richness in antioxidant agents, and factors related to the heating technique, such as duration, temperature and number of heating. Seed oils have lower antioxidant content than olive oil, especially virgin and extra virgin olive oil, making it more vulnerable to heating and generating an increase in the oxidation of lipoproteins after intake. Some options to improve the stability of fried oils include the modified fatty acid composition, such as high sunflower and medium oleic or high oleic canola and low linolenic. However, additives are a potential alternative to prevent frying oil oxidation, being able to improve its performance.
Pocos estudios se han centrado en las consecuencias biológicas del consumo de aceites de fritura. Los estudios en modelos animales han demostrado que su ingesta aumenta los niveles de lipoproteínas aterogénicas (LDL). En el ser humano, incrementa ciertos productos proaterogénicos, como la fracción oxidada de los quilomicrones y LDL. Además se ha demostrado que el contenido de compuestos polares (sustancias prooxidantes que se generan al someter al aceite a altas temperaturas) en aceites de fritura son predictivos de la hipertensión arterial. Por su parte, otros estudios han asociado el consumo de compuestos polares con la disfunción endotelial, la hipertensión, y la arteriosclerosis, y por tanto con el riesgo cardiovascular. Few studies have focused on the biological consequences of frying oil consumption. Studies in animal models have shown that their intake increases levels of atherogenic lipoproteins (LDL). In humans, it increases certain proatrogenic products, such as the oxidized fraction of chylomicrons and LDL. It has also been shown that the content of polar compounds (prooxidant substances that are generated by subjecting the oil to high temperatures) in frying oils are predictive of arterial hypertension. On the other hand, other studies have associated the consumption of polar compounds with endothelial dysfunction, hypertension, and arteriosclerosis, and therefore with cardiovascular risk.
Las consecuencias biológicas de la ingesta de aceites fritos son particularmente importantes en las personas obesas. En el medio interno de estas personas existe una inflamación sistémica crónica, de bajo grado, caracterizada por una producción anormal de citoquinas (moléculas de señalización celulares) que tienen propiedades inflamatorias y, además, se activan vías de señalización más complejas que favorecen el desarrollo de la arteriosclerosis. Esta inflamación de bajo grado se relaciona con la activación del factor NF-kB, que es el principal mediador de la respuesta inflamatoria. Su incremento refleja la activación de células mononucleares de sangre periférica (PBMC) y se asocia con la expresión de una variedad de citoquinas relacionadas con la inflamación y la respuesta inmune, fenómenos que contribuyen al desarrollo de la arteriosclerosis. The biological consequences of the intake of fried oils are particularly important in obese people. In the internal environment of these people there is a chronic systemic inflammation, of low grade, characterized by an abnormal production of cytokines (cellular signaling molecules) that have inflammatory properties and, in addition, more complex signaling pathways that favor the development of arteriosclerosis This low-grade inflammation is related to the activation of the NF-kB factor, which is the main mediator of the inflammatory response. Its increase reflects the activation of peripheral blood mononuclear cells (PBMC) and is associated with the expression of a variety of cytokines related to inflammation and immune response, phenomena that contribute to the development of arteriosclerosis.
La modulación de la respuesta inflamatoria por la dieta es uno de los principales campos de investigación actuales en nutrición y su relación con el desarrollo de enfermedades cardiovasculares. El sistema inmune sufre, a lo largo del día, numerosos episodios de activación, en relación con las distintas ingestas diarias. Tras una comida, llegan al medio interno vascular ciertos componentes potencialmente patógenos procedentes de la flora bacteriana intestinal, y/o de los alimentos ingeridos. Entre éstos destaca el lipopolisacárido (LPS), estructura común a la pared celular de múltiples bacterias y que tiene capacidad para estimular el sistema inmune y despertar una respuesta inflamatoria. Se ha demostrado que, en presencia elevada de ácidos grasos saturados en la ingesta, la cantidad de LPS y la activación subsecuente del sistema inflamatorio es mayor. Además, independientemente del tipo de grasa consumido, en las horas siguientes a una comida aumentan en sangre productos de glicación avanzada y se produce un incremento del estrés oxidativo. Todo esto puede resultar en una inflamación crónica de bajo nivel, debido a los continuos estímulos proinflamatorios derivados de la alimentación. The modulation of the inflammatory response by diet is one of the main fields of current research in nutrition and its relationship with the development of cardiovascular diseases. The immune system suffers, throughout the day, numerous activation episodes, in relation to the different daily intakes. After a meal, certain potentially pathogenic components from the intestinal bacterial flora and / or ingested food reach the vascular internal environment. Among these, the lipopolysaccharide (LPS) stands out, a structure common to the cell wall of multiple bacteria that has the capacity to stimulate the immune system and arouse an inflammatory response. It has been shown that, in the presence of saturated fatty acids in the intake, the amount of LPS and subsequent activation of the inflammatory system is greater. In addition, regardless of the type of fat consumed, in the hours following a meal, advanced glycation products increase in the blood and an increase in oxidative stress occurs. All this can result in a chronic inflammation of low level, due to the continuous proinflammatory stimuli derived from food.
Hallazgos recientes vinculan también la grasa de la dieta con la capacidad de absorción de los LPS procedentes de la flora bacteriana habitual del tubo digestivo (denominada microbiota), lo que, como hemos anteriormente, puede condicionar diferencias en el estado inflamatorio, en un mecanismo dependiente de NF-kB, a través de unos mediadores denominados receptores tipo Toll-4 (TLR4). Recent findings also link dietary fat with the ability to absorb LPS from the usual bacterial flora of the digestive tract (called microbiota), which, as we have previously, can cause differences in inflammatory status, in a dependent mechanism of NF-kB, through mediators called Toll-4 type receptors (TLR4).
En definitiva, y a pesar de que el periodo postprandial provoca una situación proinflamatoria, existen datos que demuestran que hay determinados condicionantes, como el tipo de grasa consumida o la existencia de obesidad, que provocan un aumento de este estado inflamatorio. En el caso que nos ocupa, y resumiendo también las evidencias indicadas anteriormente, la ingesta de aceite previamente frito provoca un ambiente proaterogénico, ya que produce tanto un aumento de la inflamación postprandial, debido a la existencia en ese aceite de productos proinflamatorios y prooxidantes y, además, provoca la aparición de un perfil de lipoproteínas aterogénicas en plasma. In short, and despite the fact that the postprandial period causes a pro-inflammatory situation, there are data that show that there are certain conditions, such as the type of fat consumed or the existence of obesity, which cause an increase in this inflammatory state. In the case at hand, and also summarizing the evidence indicated above, the intake of previously fried oil causes a proatrogenic environment, since it produces both an increase in postprandial inflammation, due to the existence in that oil of proinflammatory and prooxidant products and In addition, it causes the appearance of an atherogenic lipoprotein profile in plasma.
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Los autores de la presente invención han realizado un estudio para conocer si se produce una activación de NF-kB postprandial en PBMCs de personas obesas, como expresión de actividad inflamatoria, tras la ingesta aguda de cuatro diferentes aceites de fritura, con distinta composición y grasa y diferente contenido de antioxidantes, después de un proceso estandarizado de fritura. El conocimiento de las posibles diferencias de activación de NF-kB les ha permitido definir una determinada concentración de compuestos fenólicos del aceite de oliva virgen que puede prevenir la activación de los mecanismos implicados en el desarrollo de arterioesclerosis en seres humanos, y que pueden administrarse en combinación con otros aceites previamente fritos, de forma que su adición artificial en los alimentos puede reproducir los efectos biológicos presentes en el aceite que los que posee de forma natural. The authors of the present invention have carried out a study to know if postprandial NF-kB activation occurs in PBMCs of obese people, as an expression of inflammatory activity, after the acute intake of four different frying oils, with different composition and fat and different antioxidant content, after a standardized frying process. The knowledge of the possible differences in activation of NF-kB has allowed them to define a certain concentration of phenolic compounds of virgin olive oil that can prevent the activation of the mechanisms involved in the development of atherosclerosis in humans, and that can be administered in combination with other previously fried oils, so that their artificial addition in food can reproduce the biological effects present in the oil than those that it naturally possesses.
Por tanto, el uso de los compuestos fenólicos del aceite de oliva virgen en una concentración de al menos 300 ppm, y preferiblemente de 400 ppm, así como sus composiciones farmacéuticas y alimentarias, son útiles para la prevención y el tratamiento de arteriosclerosis en humanos. Therefore, the use of the phenolic compounds of virgin olive oil in a concentration of at least 300 ppm, and preferably 400 ppm, as well as their pharmaceutical and food compositions, are useful for the prevention and treatment of arteriosclerosis in humans.
Así pues, un primer aspecto de la invención se refiere al uso de los compuestos fenólicos del aceite de oliva virgen en una concentración de al menos 300 ppm, en la elaboración de una composición para la prevención o el tratamiento de la ateroesclerosis en humanos, o alternativamente, a una composición que comprende compuestos fenólicos del aceite de oliva virgen en una concentración de al menos 300 ppm para la prevención o el tratamiento de la arteriosclerosis en humanos. Thus, a first aspect of the invention relates to the use of the phenolic compounds of virgin olive oil in a concentration of at least 300 ppm, in the preparation of a composition for the prevention or treatment of atherosclerosis in humans, or alternatively, to a composition comprising phenolic compounds of virgin olive oil in a concentration of at least 300 ppm for the prevention or treatment of arteriosclerosis in humans.
En una realización preferida de la presente invención, los compuestos fenólicos del aceite de oliva virgen se encuentran en una concentración de al menos 350 ppm, y más preferiblemente, se encuentran en una concentración de al menos 400 ppm. In a preferred embodiment of the present invention, the phenolic compounds of the virgin olive oil are in a concentration of at least 350 ppm, and more preferably, they are in a concentration of at least 400 ppm.
En otra realización preferida, los compuestos fenólicos del aceite de oliva virgen se obtienen del alperujo. En otra realización preferida, el humano presenta un índice de masa corporal (IMC) mayor o igual a 24 kg/m2. In another preferred embodiment, the phenolic compounds of virgin olive oil are obtained from the alperujo. In another preferred embodiment, the human has a body mass index (BMI) greater than or equal to 24 kg / m2.
El término “compuestos fenólicos” del aceite de oliva virgen, se refiere a un conjunto de fenoles entre los que se encuentran, pero sin limitarse a ellos, tirosol, apigenina, luteolina ácido vainilinico, ácido p-cumárico, oleuropeína y oleuropeína aglicona. The term "phenolic compounds" of virgin olive oil, refers to a set of phenols among which are, but not limited to, tyrosol, apigenin, luteinoline vanillinic acid, p-cumaric acid, oleuropein and oleuropein aglycone.
En otra realización preferida, la composición es una composición farmacéutica o medicamento. Más preferiblemente, la composición farmacéutica comprende además un vehículo farmacéuticamente aceptable, y aún más preferiblemente, la composición farmacéutica comprende, además, otro principio activo. In another preferred embodiment, the composition is a pharmaceutical composition or medicament. More preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, and even more preferably, the pharmaceutical composition further comprises another active ingredient.
El término “medicamento”, tal y como se usa en esta memoria, hace referencia a cualquier sustancia usada para prevención, diagnóstico, alivio, tratamiento o curación de enfermedades en el hombre y los animales. En el contexto de la presente invención, la enfermedad es la arteriosclerosis. The term "medication", as used herein, refers to any substance used for prevention, diagnosis, relief, treatment or cure of diseases in man and animals. In the context of the present invention, the disease is arteriosclerosis.
Como se emplea aquí, el término “principio activo”, “substancia activa”, “substancia farmacéuticamente activa”, “ingrediente activo” o “ingrediente farmacéuticamente activo” significa cualquier componente que potencialmente proporcione una actividad farmacológica u otro efecto diferente en el diagnóstico, cura, mitigación, tratamiento, o prevención de una enfermedad, o que afecte a la estructura o función del cuerpo del hombre u otros animales. El término incluye aquellos componentes que promueven un cambio químico en la elaboración del fármaco y están presentes en el mismo de una forma modificada prevista que proporciona la actividad específica o el efecto. As used herein, the term "active substance", "active substance", "pharmaceutically active substance", "active ingredient" or "pharmaceutically active ingredient" means any component that potentially provides a pharmacological activity or other different effect on the diagnosis, cure, mitigation, treatment, or prevention of a disease, or that affects the structure or function of the body of man or other animals. The term includes those components that promote a chemical change in the preparation of the drug and are present therein in a modified form intended to provide the specific activity or effect.
Las composiciones de la presente invención pueden formularse para su administración a un animal, y más preferiblemente a un mamífero, incluyendo al hombre, en una variedad de formas conocidas en el estado de la técnica. Así, pueden estar, sin limitarse, en disolución acuosa estéril o en fluidos biológicos, tal como suero. Las disoluciones acuosas pueden estar tamponadas o no tamponadas y contener componentes activos o inactivos adicionales. Los componentes adicionales incluyen sales para modular la fuerza iónica, conservantes incluyendo, pero sin limitarse, agentes antimicrobianos, antioxidantes, quelantes y similares, así como nutrientes incluyendo glucosa, dextrosa, vitaminas y minerales. Alternativamente, las composiciones pueden prepararse para su administración en forma sólida. Las composiciones pueden combinarse con varios vehículos o excipientes inertes, incluyendo pero sin limitarse a; aglutinantes tales como celulosa microcristalina, goma tragacanto, o gelatina; excipientes tales como almidón o lactosa; agentes dispersantes tales como ácido algínico o almidón de maíz; lubricantes tales como estearato de magnesio, deslizantes tales como dióxido de silicio coloidal; agentes edulcorantes tales como sacarosa o sacarina; o agentes aromatizantes tales como menta o salicilato de metilo. The compositions of the present invention can be formulated for administration to an animal, and more preferably to a mammal, including man, in a variety of ways known in the state of the art. Thus, they can be, without limitation, in sterile aqueous solution or in biological fluids, such as serum. Aqueous solutions may be buffered or unbuffered and contain additional active or inactive components. Additional components include salts to modulate ionic strength, preservatives including, but not limited to, antimicrobial agents, antioxidants, chelants and the like, as well as nutrients including glucose, dextrose, vitamins and minerals. Alternatively, the compositions can be prepared for administration in solid form. The compositions may be combined with various inert vehicles or excipients, including but not limited to; binders such as microcrystalline cellulose, gum tragacanth, or gelatin; excipients such as starch or lactose; dispersing agents such as alginic acid or corn starch; lubricants such as magnesium stearate, glidants such as colloidal silicon dioxide; sweetening agents such as sucrose or saccharin; or flavoring agents such as peppermint or methyl salicylate.
Tales composiciones y/o sus formulaciones pueden administrarse a un animal, incluyendo un mamífero y, por tanto, al hombre, en una variedad de formas, incluyendo, pero sin limitarse a, intraperitoneal, intravenoso, intramuscular, subcutáneo, intracecal, intraventricular, oral, enteral, parenteral, intranasal o dérmico. Preferiblemente, la vía de administración es oral. Such compositions and / or their formulations may be administered to an animal, including a mammal and, therefore, to man, in a variety of ways, including, but not limited to, intraperitoneal, intravenous, intramuscular, subcutaneous, intracecal, intraventricular, oral. , enteral, parenteral, intranasal or dermal. Preferably, the route of administration is oral.
La dosificación para obtener una cantidad terapéuticamente efectiva depende de una variedad de factores, como, por ejemplo, la edad, peso, sexo o tolerancia, del mamífero. En el sentido utilizado en esta descripción, la expresión "cantidad terapéuticamente efectiva" se refiere a la cantidad de compuestos fenólicos del aceite de oliva virgen que produzcan el efecto deseado y, en general, vendrá determinada, entre otras causas, por las características propias del aceite de oliva virgen, así como del resto de los componentes de la composición, y el efecto terapéutico a conseguir. Los “adyuvantes” y “vehículos farmacéuticamente aceptables” que pueden ser utilizados en dichas composiciones son los vehículos conocidos por los técnicos en la materia. The dosage to obtain a therapeutically effective amount depends on a variety of factors, such as, for example, age, weight, sex or tolerance, of the mammal. In the sense used in this description, the term "therapeutically effective amount" refers to the amount of phenolic compounds in virgin olive oil that produce the desired effect and, in general, will be determined, among other causes, by the characteristics of the virgin olive oil, as well as the rest of the components of the composition, and the therapeutic effect to be achieved. The "adjuvants" and "pharmaceutically acceptable carriers" that can be used in said compositions are the vehicles known to those skilled in the art.
El término “excipiente” hace referencia a una sustancia que ayuda a la absorción, distribución o acción de cualquiera de los principios activos de la presente invención, estabiliza dicha sustancia activa o ayuda a la preparación del medicamento en el sentido de darle consistencia o aportar sabores que lo hagan más agradable. Así pues, los excipientes podrían tener la función de mantener los ingredientes unidos, como, por ejemplo, almidones, azúcares o celulosas, función de endulzar, función de colorante, función de protección del medicamento, como, por ejemplo, para aislarlo del aire y/o la humedad, función de relleno de una pastilla, cápsula o cualquier otra forma de presentación como por ejemplo el fosfato de calcio dibásico, función desintegradora para facilitar la disolución de los componentes y su absorción en el intestino, sin excluir otro tipo de excipientes no mencionados en este párrafo. The term "excipient" refers to a substance that aids the absorption, distribution or action of any of the active ingredients of the present invention, stabilizes said active substance or aids in the preparation of the medicament in the sense of giving it consistency or providing flavors. Make it more enjoyable. Thus, the excipients could have the function of keeping the ingredients together, such as, for example, starches, sugars or celluloses, sweetening function, coloring function, protection function of the medicine, such as for example isolating it from the air and / or moisture, filling function of a tablet, capsule or any other form of presentation such as dibasic calcium phosphate, a disintegrating function to facilitate the dissolution of the components and their absorption in the intestine, without excluding other types of excipients not mentioned in this paragraph.
El término excipiente “farmacéuticamente aceptable” hace referencia a que el excipiente esté permitido y evaluado de modo que no cause daño a los organismos a los que se administra. The term "pharmaceutically acceptable" excipient refers to the excipient being allowed and evaluated so as not to cause damage to the organisms to which it is administered.
Además, el excipiente debe ser farmacéuticamente adecuado, es decir, un excipiente que permita la actividad del principio activo o de los principios activos, es decir, que sea compatible con el principio activo, en este caso, el principio activo es cualquiera de los compuestos de la presente invención. In addition, the excipient must be pharmaceutically suitable, that is, an excipient that allows the activity of the active ingredient or of the active ingredients, that is, that is compatible with the active ingredient, in this case, the active ingredient is any of the compounds of the present invention.
Un “vehículo farmacéuticamente aceptable” se refiere a aquellas sustancias, o combinación de sustancias, conocidas en el sector farmacéutico, utilizadas en la elaboración de formas farmacéuticas de administración e incluye, pero sin limitarse, sólidos, líquidos, disolventes o tensioactivos. A "pharmaceutically acceptable carrier" refers to those substances, or combination of substances, known in the pharmaceutical sector, used in the preparation of pharmaceutical forms of administration and includes, but are not limited to, solids, liquids, solvents or surfactants.
El vehículo, al igual que el excipiente, es una sustancia que se emplea en el medicamento para diluir cualquiera de los compuestos de la presente invención hasta un volumen o peso determinado. El vehículo farmacéuticamente aceptable es una sustancia inerte o de acción análoga a cualquiera de las células de la presente invención. La función del vehículo es facilitar la incorporación de otros compuestos, permitir una mejor dosificación y administración o dar consistencia y forma a la composición farmacéutica. Cuando la forma de presentación es líquida, el vehículo farmacéuticamente aceptable es el diluyente. The vehicle, like the excipient, is a substance that is used in the medicament to dilute any of the compounds of the present invention to a certain volume or weight. The pharmaceutically acceptable carrier is an inert substance or action analogous to any of the cells of the present invention. The function of the vehicle is to facilitate the incorporation of other compounds, allow a better dosage and administration or give consistency and form to the pharmaceutical composition. When the form of presentation is liquid, the pharmaceutically acceptable carrier is the diluent.
En otra realización preferida la composición es una composición alimentaria. Más preferiblemente, la composición alimentaria comprende un suplemento nutricional. Aún más preferiblemente, la composición comprende una matriz alimentaria. En otra realización preferida, la matriz alimentaria se selecciona de la lista que comprende: leche, yogurt, queso, leche fermentada, leche de soja, cereales precocinados, galletas, pan, bollos, mantequilla, margarina, salchichas, aceites de freír, aceites vegetales, condimentos, zumos de frutas, siropes, helados, productos congelado, gomas de mascar y alimentos intermedios. In another preferred embodiment the composition is a food composition. More preferably, the food composition comprises a nutritional supplement. Even more preferably, the composition comprises a food matrix. In another preferred embodiment, the food matrix is selected from the list comprising: milk, yogurt, cheese, fermented milk, soy milk, pre-cooked cereals, cookies, bread, buns, butter, margarine, sausages, frying oils, vegetable oils , condiments, fruit juices, syrups, ice cream, frozen products, chewing gums and intermediate foods.
En otra realización preferida la matriz alimentaria es un aceite vegetal o una mezcla de aceites vegetales. Más preferiblemente, el aceite vegetal es aceite de girasol. La mezcla de aceites vegetales comprende: aceite de girasol alto oleico y aceite de colza. En otra realización más preferida la mezcla de aceites vegetales comprende: aceite de girasol alto oleico y aceite de colza. In another preferred embodiment the food matrix is a vegetable oil or a mixture of vegetable oils. More preferably, the vegetable oil is sunflower oil. The mixture of vegetable oils comprises: high oleic sunflower oil and rapeseed oil. In another more preferred embodiment the mixture of vegetable oils comprises: high oleic sunflower oil and rapeseed oil.
Otro aspecto de la invención se refiere al uso de una composición de la invención (la composición alimentaria o la composición farmacéutica), para prevenir la generación de un ambiente proaterogénico en el endotelio. Another aspect of the invention relates to the use of a composition of the invention (the food composition or the pharmaceutical composition), to prevent the generation of a pro-endogenous environment in the endothelium.
Otro aspecto de la invención se refiere al uso de la composición alimentaria de la invención en la elaboración de un medicamento para la prevención o el tratamiento de la arterioesclerosis, preferentemente en humanos. Another aspect of the invention relates to the use of the food composition of the invention in the preparation of a medicament for the prevention or treatment of atherosclerosis, preferably in humans.
A lo largo de la descripción y las reivindicaciones la palabra "comprende" y sus variantes no pretenden excluir otras características técnicas, aditivos, componentes o pasos. Para los expertos en la materia, otros objetos, ventajas y características de la invención se desprenderán en parte de la descripción y en parte de la práctica de la invención. Los siguientes ejemplos y dibujos se proporcionan a modo de ilustración, y no se pretende que sean limitativos de la presente invención. Throughout the description and the claims the word "comprises" and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and features of the invention will be derived partly from the description and partly from the practice of the invention. The following examples and drawings are provided by way of illustration, and are not intended to be limiting of the present invention.
Figura 1 A: Análisis cuantitativo de la activación postprandial de NF-KB, en células mononucleares de sangre periférica, de las personas que recibieron cuatro modelos de desayuno, con productos de bollería elaborados con distintos tipos de aceites. Puede verse que solo los aceites con polifenoles VOO (Aceite de oliva virgen) y SOP (Aceite vegetal añadido con polifenoles) redujeron la expresión del NF-KB, reflejando que evitaron el estado proinflamatorio inducido por los otros aceites (SFO (Aceite de girasol) y SOD (Aceite de semilla con Dimetilpolisiloxano). Figure 1 A: Quantitative analysis of postprandial activation of NF-KB, in peripheral blood mononuclear cells, of people who received four breakfast models, with pastry products made with different types of oils. It can be seen that only oils with polyphenols VOO (virgin olive oil) and SOP (vegetable oil added with polyphenols) reduced the expression of NF-KB, reflecting that they avoided the pro-inflammatory state induced by the other oils (SFO (Sunflower oil) and SOD (Seed oil with Dimethylpolysiloxane).
Figura 1B: Análisis cuantitativo de la activación postprandial de IKB-a, en células mononucleares de sangre periférica, de las personas que recibieron cuatro modelos de desayuno, con productos de bollería elaborados con distintos tipos de aceites. Su incremento con los aceites con polifenoles VOO (Aceite de oliva virgen) y SOP (Aceite vegetal añadido con polifenoles) se interpreta como una capacidad de estos aceites para amortiguar la respuesta inflamatoria dependiente Figure 1B: Quantitative analysis of the postprandial activation of IKB-a, in peripheral blood mononuclear cells, of people who received four breakfast models, with pastry products made with different types of oils. Its increase with oils with polyphenols VOO (virgin olive oil) and SOP (vegetable oil added with polyphenols) is interpreted as a capacity of these oils to buffer the dependent inflammatory response
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de la activación del NF-KB. of the activation of the NF-KB.
Figura 2: A las dos horas de la ingesta de los desayunos, con distinto contenido de aceites, se observó que con los aceites ricos en polifenoles (VOO y SOP) no se incrementan los niveles de Lipopolisacárido plasmático (LPS), señalando que no existe una absorción intestinal de dicho componente bacteriano. Figure 2: Two hours after the breakfast intake, with different oil content, it was observed that with the oils rich in polyphenols (VOO and SOP) the levels of plasma Lipopolysaccharide (LPS) are not increased, indicating that there is no an intestinal absorption of said bacterial component.
Se realizó un ensayo clínico que se describe a continuación, y que pone de manifiesto la especificidad y efectividad de los compuestos fenólicos del aceite de oliva virgen en una determinada concentración en la prevención de la activación inflamatoria que favorece el desarrollo de la arterioesclerosis en humanos. A clinical trial was described and described below, which shows the specificity and effectiveness of the phenolic compounds of virgin olive oil in a certain concentration in the prevention of inflammatory activation that favors the development of atherosclerosis in humans.
MATERIALES Y MÉTODOS MATERIALS AND METHODS
El estudio se realizó en veinte obesos sanos (edad media de 56 años, rango entre 40–70). Todos ellos firmaron su consentimiento informado y se les realizó una historia médica completa, examen físico y análisis de química clínica antes de la inscripción. Tenían un índice de masa corporal (IMC) promedio de 37,3 (29,4-44,9) kg/m2, perímetro de cintura de 113,7 cm (88–145), los niveles plasmáticos de colesterol total (CT) de 201.1 ± 3.8 mg/dl, los niveles plasmáticos de triglicéridos (TG) 102.9 ± 3.6 mg/dl, los niveles de colesterol de lipoproteínas de baja densidad (LDLc) de The study was conducted in twenty healthy obese people (mean age of 56 years, range 40–70). All of them signed their informed consent and had a complete medical history, physical examination and clinical chemistry analysis before enrollment. They had an average body mass index (BMI) of 37.3 (29.4-44.9) kg / m2, waist circumference of 113.7 cm (88-145), plasma levels of total cholesterol (CT) of 201.1 ± 3.8 mg / dl, plasma triglyceride levels (TG) 102.9 ± 3.6 mg / dl, low density lipoprotein cholesterol (LDLc) levels of
130.2 ± 3.0 mg/dL y los niveles de colesterol de las lipoproteínas de alta densidad (HDLc) de 50.8 ± 1.2 mg/dl, niveles de glucosa plasmática de 100.9 ± 0.9 mg/dL y niveles de insulina de 10.7 ± 0.5 mU/L. Ninguno de los participantes mostraron indicios de enfermedades crónicas (hepática, renal, tiroides, corazón). Todos fueron no diabéticos, no fumadores, sin manifestación clínica de enfermedad cardiovascular y sin tratamiento. Ninguno tomaba medicamentos o vitaminas que se conozca que afectan a los lípidos plasmáticos. El protocolo del estudio fue aprobado por la Comisión de Investigación del Hospital Universitario Reina Sofía, de acuerdo con el marco institucional y las Directrices de Buenas Prácticas Clínicas. 130.2 ± 3.0 mg / dL and high density lipoprotein (HDLc) cholesterol levels of 50.8 ± 1.2 mg / dL, plasma glucose levels of 100.9 ± 0.9 mg / dL and insulin levels of 10.7 ± 0.5 mU / L . None of the participants showed signs of chronic diseases (liver, kidney, thyroid, heart). All were non-diabetic, non-smokers, without clinical manifestation of cardiovascular disease and without treatment. None took medications or vitamins that are known to affect plasma lipids. The study protocol was approved by the Research Commission of the Reina Sofía University Hospital, in accordance with the institutional framework and the Guidelines of Good Clinical Practices.
Todos los voluntarios recibieron cuatro desayunos con magdalenas elaboradas con cuatro aceites diferentes. Cada desayuno contenía 0,45 ml de aceite y 40 equivalentes de retinol, por kilogramo de peso corporal, y una distribución de calorías de 56% de grasas, 9% de proteínas y 35% de hidratos de carbono. Los desayunos eran administrados con un diseño aleatorizado y cruzado, siguiendo un modelo de cuadrado latino, lo que aumentó el poder del estudio. Los voluntarios fueron divididos en cuatro grupos de forma aleatoria y estratificada por sexo para recibir cada desayuno con un periodo de lavado de dos semanas entre cada uno de ellos. Los aceites fueron sometidos previamente a un proceso de fritura estandarizado (20 ciclos de calentamiento a 180 ºC durante 5 minutos por ciclo). Los aceites utilizados en el desayuno, así como su composición, son los siguientes: All volunteers received four breakfasts with muffins made with four different oils. Each breakfast contained 0.45 ml of oil and 40 equivalents of retinol, per kilogram of body weight, and a calorie distribution of 56% fat, 9% protein and 35% carbohydrates. The breakfasts were administered with a randomized and crossed design, following a Latin square model, which increased the power of the study. The volunteers were divided into four groups randomly and stratified by sex to receive each breakfast with a two-week wash period between each of them. The oils were previously subjected to a standardized frying process (20 heating cycles at 180 ° C for 5 minutes per cycle). The oils used for breakfast, as well as their composition, are the following:
- 1. one.
- Aceite de oliva virgen (VOO) con 400 ppm de antioxidantes fenólicos naturales: 70,5% ácidos grasos monoinsaturados (MONO), 11,1% de ácidos grasos poliinsaturados (POLI) y 18,4% de ácidos grasos saturados (SAT), Virgin olive oil (VOO) with 400 ppm of natural phenolic antioxidants: 70.5% monounsaturated fatty acids (MONO), 11.1% polyunsaturated fatty acids (POLI) and 18.4% saturated fatty acids (SAT),
- 2. 2.
- Aceite de girasol (SFO): 34,3% MONO, 58,3% de POLI y 7.3% de SAT. Sunflower oil (SFO): 34.3% MONO, 58.3% POLI and 7.3% SAT.
- 3. 3.
- Mezcla de aceites de semillas mixta (30% de girasol alto oleico y 70% de aceite de colza) enriquecido con 2 mg/kg de dimetilpolisiloxano antioxidante (SOD): 71,8% de MONO, 18,0% de POLI y 10,2% SAT. Mixture of mixed seed oils (30% high oleic sunflower and 70% rapeseed oil) enriched with 2 mg / kg antioxidant dimethylpolysiloxane (SOD): 71.8% MONO, 18.0% POLI and 10, 2% SAT
- 4. Four.
- Mezcla de aceites y semillas (30% de girasol alto oleico y 70% de aceite de colza) enriquecido con 400 ppm de compuestos fenoles extraídos del residuo de la producción de aceite de oliva-alperujo (SOP): 76,7% de MONO, 17,6% de POLI y 5,8% de SAT. Mixture of oils and seeds (30% high oleic sunflower and 70% rapeseed oil) enriched with 400 ppm of phenolic compounds extracted from the olive-olive oil production residue (SOP): 76.7% of MONO, 17.6% of POLI and 5.8% of SAT.
Enriquecimiento de los aceites con fenoles extraídos de alperujo. Enrichment of oils with phenols extracted from alperujo.
Se realizó con el método de Girón et al. (2009. J Agric Food Chem 57(7): p. 2797-802), basado en extracción sólido– líquido (S–L). Un volumen de extracto de alperujo se puso en contacto con 3 ml de aceite y se agitó vigorosamente durante 30 min. Transcurrido este tiempo, la fase etanol–agua se separó por centrifugación a 3000 rpm durante 10 min. El aceite enriquecido resultante se analizó para determinar la concentración de fenoles totales e individuales. It was performed with the method of Girón et al. (2009. J Agric Food Chem 57 (7): p. 2797-802), based on solid-liquid extraction (S – L). A volume of alperujo extract was contacted with 3 ml of oil and stirred vigorously for 30 min. After this time, the ethanol-water phase was separated by centrifugation at 3000 rpm for 10 min. The resulting enriched oil was analyzed to determine the concentration of total and individual phenols.
Procedimiento de fritura. Dos litros de cada aceite se colocó en una freidora inoxidable y se sometió a 20 ciclos de calentamiento (a 180 º C ± 5 º C durante 5 minutos/ciclo). Frying procedure Two liters of each oil was placed in a stainless fryer and subjected to 20 heating cycles (at 180 º C ± 5 º C for 5 minutes / cycle).
La concentración de fenoles en los aceites enriquecidos se determinó tanto de forma global (método de Folin– Ciocalteu), como individual (separación cromatográfica y detección mediante espectrometría de absorción molecular — HPLC–DAD) después de la extracción de los analitos seleccionados. The concentration of phenols in the enriched oils was determined both globally (Folin-Ciocalteu method), and individually (chromatographic separation and detection by molecular absorption spectrometry - HPLC-DAD) after extraction of the selected analytes.
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Extracción de los compuestos fenólicos del aceite. Alícuotas de aceite de 2 g se agitaron durante 30 min con 20 ml de metanol y 2 ml de hexano. La fase de metanol, que contiene los compuestos fenólicos, se separó por centrifugación, se evaporó hasta la preconcentración adecuada y se almacenó a –20 º C hasta su posterior análisis. Extraction of phenolic compounds from oil. 2 g aliquots of oil were stirred for 30 min with 20 ml of methanol and 2 ml of hexane. The methanol phase, which contains the phenolic compounds, was separated by centrifugation, evaporated until adequate preconcentration and stored at -20 ° C until further analysis.
Separación y cuantificación mediante HPLC–DAD. El método aplicado fue el propuesto por el Consejo Oleícola Internacional (COI) para la determinación individual de los compuestos fenólicos del aceite de oliva. La columna analítica empleada fue una Inertisil ODS-2 de fase reversa de 250 × 4 mm i.d., 5 μm; el volumen de inyección de 10 μl y la fase móvil una mezcla de A (agua acidificada con 0,2% de ácido fosfórico) y B (acetonitrilo- metanol, 1:1 v / v) a 1 ml/min. Una elución lineal inicial en gradiente de 0 a 50% B en 40 minutos fue seguido por otros gradiente de elución lineal de 50 a 60% B en 5 minutos y un tercer gradiente de 60 a 100% B en 10 minutos. Por último, el instrumento fue mantenido en condiciones isocráticas (100% B) durante 2 min. Es necesaria una etapa de equilibración de 5 minutos para restablecer las condiciones iniciales y alcanzar la estabilización de la fase móvil. Los fenoles eluídos se midieron a 230, 280, 325 y 350 nm (tiempo de elución total inferior a 57 min). Separation and quantification by HPLC-DAD. The method applied was that proposed by the International Olive Council (IOC) for the individual determination of phenolic compounds in olive oil. The analytical column used was a reverse phase IDS-2 Inertisil of 250 × 4 mm i.d., 5 μm; the injection volume of 10 μl and the mobile phase a mixture of A (water acidified with 0.2% phosphoric acid) and B (acetonitrilemethanol, 1: 1 v / v) at 1 ml / min. An initial linear elution in gradient from 0 to 50% B in 40 minutes was followed by other linear elution gradient from 50 to 60% B in 5 minutes and a third gradient from 60 to 100% B in 10 minutes. Finally, the instrument was kept in isocratic conditions (100% B) for 2 min. A 5 minute equilibration stage is necessary to restore the initial conditions and achieve stabilization of the mobile phase. Eluted phenols were measured at 230, 280, 325 and 350 nm (total elution time less than 57 min).
Muestras de sangre y aislamiento de PMBCs Blood samples and isolation of PMBCs
Se obtuvieron muestras de sangre venosa (40 ml) en tubos con EDTA tras 12 horas de ayuno y a las 4 horas después de la ingestión del desayuno. Las muestras se diluyeron 1:1 en PBS, y las células se separaron en 15 ml de gradiente de Ficoll (solución de aislamiento de linfocitos, Rafer) por centrifugación 800 x g durante 25 min. La fase de PBMCs se extrajo con pipeta Pasteur, se lavó dos veces con PBS frío y se suspendió en solución tampón de lisis [10 mM de N-2 10 mM de N-2 hidroxietil piperazina ácido-N'-2-etano (HEPES), pH 7,5, 15 mM KCl, 0.1 mM EDTA, 2 MgCl2, 1 mM ditiotreitol (TDT), 1 mM de fluoruro de fenilmetilsulfonilo (PMSF). Samples of venous blood (40 ml) were obtained in EDTA tubes after 12 hours of fasting and at 4 hours after breakfast ingestion. The samples were diluted 1: 1 in PBS, and the cells were separated in 15 ml of Ficoll gradient (lymphocyte isolation solution, Rafer) by centrifugation 800 x g for 25 min. The PBMCs phase was extracted with Pasteur pipette, washed twice with cold PBS and suspended in lysis buffer [10 mM of 10 mM N-2 N-2 hydroxyethyl piperazine acid-N'-2-ethane (HEPES ), pH 7.5, 15 mM KCl, 0.1 mM EDTA, 2 MgCl2, 1 mM dithiothreitol (DTT), 1 mM phenylmethylsulfonyl fluoride (PMSF).
Análisis de lípidos y determinaciones bioquímicas Lipid analysis and biochemical determinations
Los parámetros lipídicos se midieron con un autoanalizador modular DDPPII Hitachi (Roche, Basel, Switzerland) utilizando reactivos específicos (Boehringer-Mannheim, Mannheim, Germany). Los triglicéridos (TG) y el colesterol total (CT) se midió por métodos colorimétricos enzimáticos y el colesterol HDL (C-HDL) por métodos enzimáticos. El colesterol LDL (C-LDL) se calculó por la formula de Friedewald basada en los valores de CT, TG, y C-HDL. Las concentraciones de glucosa plasmática se midieron en un analizador Hitachi 917 (Boehringer Mannheim, Mannheim, Germany) por el método de la glucosa oxidasa (GOD-PAP). Lipid parameters were measured with a Hitachi DDPPII modular autoanalyzer (Roche, Basel, Switzerland) using specific reagents (Boehringer-Mannheim, Mannheim, Germany). Triglycerides (TG) and total cholesterol (CT) were measured by enzymatic colorimetric methods and HDL (C-HDL) cholesterol by enzymatic methods. LDL cholesterol (C-LDL) was calculated by Friedewald's formula based on the values of CT, TG, and C-HDL. Plasma glucose concentrations were measured on a Hitachi 917 analyzer (Boehringer Mannheim, Mannheim, Germany) by the glucose oxidase method (GOD-PAP).
Extracción de la proteína nuclear Nuclear Protein Extraction
Las células se resuspendieron en tampón de lisis celular, se descongelaron y se lisaron en hielo durante 10 minutos. Los tubos se agitaron para romper las membranas celulares y se centrifugaron a 16 000 x g a 4 ° C durante 5 min. Luego se resuspendieron en solución tampón de lisis celular (10 mM HEPES, pH 7,5, 10 mM KCl, 0.1 mM EDTA, 1 mM DTT, 0,5% NonidetP - 40 y 0,5 mM PMSF) y se mantuvieron en hielo durante 10 minutos, siendo finalmente centrifugadas a 16 000 x g a 4 º C durante 5 min. Los sobrenadantes se almacenaron como extractos citoplasmáticos. Los pellets que contienen la fracción nuclear se resuspendieron en tampón de extracción nuclear [20 mM de HEPES (pH 7,5), 400 mM NaCl, 1 mM EDTA, 1 mM DTT, 1 mM PMSF] y se incubaron en hielo durante 20 min. A continuación, la suspensión se centrifugó a 16 000 x g durante 15 min a 4 ° C y del sobrenadante se recogió el extracto nuclear. La concentración de proteínas fue estimada utilizando el reactivo de Bradford (Bio-Rad). The cells were resuspended in cell lysis buffer, thawed and lysed on ice for 10 minutes. The tubes were shaken to break the cell membranes and centrifuged at 16,000 x g at 4 ° C for 5 min. They were then resuspended in cell lysis buffer solution (10 mM HEPES, pH 7.5, 10 mM KCl, 0.1 mM EDTA, 1 mM DTT, 0.5% NonidetP-40 and 0.5 mM PMSF) and kept on ice for 10 minutes, being finally centrifuged at 16,000 xga at 4 ° C for 5 min. Supernatants were stored as cytoplasmic extracts. Pellets containing the nuclear fraction were resuspended in nuclear extraction buffer [20 mM HEPES (pH 7.5), 400 mM NaCl, 1 mM EDTA, 1 mM DTT, 1 mM PMSF] and incubated on ice for 20 min . Then, the suspension was centrifuged at 16,000 x g for 15 min at 4 ° C and the nuclear extract was collected from the supernatant. Protein concentration was estimated using Bradford reagent (Bio-Rad).
Ensayos de movilidad electroforética Shift (EMSA) Shift electrophoretic mobility tests (EMSA)
Los extractos nucleares fueron testados mediante su capacidad de unión con NF-kB, utilizando oligonucleótidos consenso SEQ ID NO: 1 y SEQ ID NO: 3, de Santa Cruz Biotechnology, utilizando el kit de Digoxigenina EMSA de Roche Diagnostics (Basilea, Suiza). Un total de 15 μg de proteína nuclear fueron tratados de acuerdo con las instrucciones del kit. Los complejos se detectaron con el sustrato quimioluminiscente CSPD y fueron expuestos a Hyperfilm de Amersham Biosciences, en un soporte de película de 4 – 16 horas a temperatura ambiente. Nuclear extracts were tested by means of their binding capacity with NF-kB, using consensus oligonucleotides SEQ ID NO: 1 and SEQ ID NO: 3, from Santa Cruz Biotechnology, using the EMSA Digoxigenin kit from Roche Diagnostics (Basel, Switzerland). A total of 15 μg of nuclear protein were treated according to the kit instructions. The complexes were detected with the CSPD chemiluminescent substrate and were exposed to Amersham Biosciences Hyperfilm, on a film support 4-16 hours at room temperature.
Western Blotting Western blotting
Los extractos citoplasmáticos (70 μg) se resuspendieron en un gel de poliacrilamida (SDS-PAGE) de electroforesis al 12% de dodecil sulfato sódico y posteriormente se transfirieron a membranas de nitrocelulosa en Tris 25 mM, glicina 192 mM, metanol al 20% y se sometieron a 15 V durante 1 hora usando transferencia semi-seca y siguiendo los protocolos estándar. La cantidad de proteína transferida se comprobó utilizando la solución de mancha Ponceau-S en 1% de ácido acético. Los sitios de unión inespecífica se bloquearon por incubación de la membrana en TTBS (25 mM Tris HCl, 150 mM NaCl, 0.05% Tween-20, pH 7,6), con 5% de leche en polvo. Las membranas se incubaron durante una noche a 4 °C con anticuerpos primarios policlonales anti-IKB-a (Santa Cruz Biotechnology) (1:200 en 5% de leche descremada en polvo en TTBS). La membrana se lavó con TTBS y se incubó con el anticuerpo secundario [IgG anti-conejo, conjugado con HRP (Biotecnología Santa Cruz) (1:1000 en 5% de leche en polvo en TTBS)] durante 1 hora a temperatura ambiente. Después de un lavado con TTBS, las proteínas se detectaron mediante el kit de quimioluminiscencia del reactivo Luminol Reagent detection system (Santa Cruz Biotechnology). Los niveles de proteína se cuantificaron con el densitómetro calibrado SG-800 (Bio-Rad) y fueron analizados con el Quantity One 4.6.5 software. Los resultados fueron calculados en términos de densidad óptica integrada (IOD) normailizada según el método de tinción con rojo Ponceau S y se expresaron en unidades arbitrarias (UA). The cytoplasmic extracts (70 μg) were resuspended in a 12% polyacrylamide (SDS-PAGE) electrophoresis gel of sodium dodecyl sulfate and subsequently transferred to 25 mM Tris nitrocellulose membranes, 192 mM glycine, 20% methanol and They were subjected to 15 V for 1 hour using semi-dry transfer and following standard protocols. The amount of protein transferred was checked using the Ponceau-S stain solution in 1% acetic acid. The nonspecific binding sites were blocked by incubation of the membrane in TTBS (25 mM Tris HCl, 150 mM NaCl, 0.05% Tween-20, pH 7.6), with 5% milk powder. The membranes were incubated overnight at 4 ° C with primary polyclonal anti-IKB-a antibodies (Santa Cruz Biotechnology) (1: 200 in 5% skim milk powder in TTBS). The membrane was washed with TTBS and incubated with the secondary antibody [anti-rabbit IgG, conjugated with HRP (Santa Cruz Biotechnology) (1: 1000 in 5% milk powder in TTBS)] for 1 hour at room temperature. After a TTBS wash, the proteins were detected by the chemiluminescence kit of the Luminol Reagent detection system reagent (Santa Cruz Biotechnology). Protein levels were quantified with the SG-800 calibrated densitometer (Bio-Rad) and analyzed with the Quantity One 4.6.5 software. The results were calculated in terms of integrated optical density (IOD) standardized according to the Ponceau S red staining method and expressed in arbitrary units (UA).
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La endotoxinas (LPS) se midieron mediante una prueba de lisado de amebocitos de Limulus (QCL-1000; Lonza Ibérica, SA Barcelona, España), según lo recomendado por el fabricante. Se recolectó el suero en tubos no pirogénicos y se congeló a –20 °C hasta el ensayo. Todos los procedimientos fueron realizados en condiciones no pirogénicas. El suero fue diluido al 1:5, mezclados con lisado de amebocitos de Limulus (LAL) y fue incubado a 37 ºC durante 10 minutos. Una solución de sustrato se mezcló con la muestra LAL y se incubó a 37 ºC durante 6 minutos. La reacción se detuvo con el reactivo de parada. Cuando la endotoxina está presente en el suero, se desarrolla un color amarillo. La absorbancia de la solución coloreada se leyó a 405 nm. La recuperación de lipopolisacárido fue de entre 50 y 200%. La sensibilidad del ensayo fue de 0,005 unidades Ehrlich/ml (0,5 pg/ml). Los coeficientes intra- e inter-ensayo de variación para la determinación de LPS fueron entre 5–10%. Endotoxins (LPS) were measured by a Limulus amebocyte lysate test (QCL-1000; Lonza Ibérica, SA Barcelona, Spain), as recommended by the manufacturer. Serum was collected in non-pyrogenic tubes and frozen at -20 ° C until assay. All procedures were performed under non-pyrogenic conditions. The serum was diluted 1: 5, mixed with Limulus amebocyte lysate (LAL) and incubated at 37 ° C for 10 minutes. A substrate solution was mixed with the LAL sample and incubated at 37 ° C for 6 minutes. The reaction was stopped with the stop reagent. When endotoxin is present in the serum, a yellow color develops. The absorbance of the colored solution was read at 405 nm. The recovery of lipopolysaccharide was between 50 and 200%. The sensitivity of the assay was 0.005 Ehrlich units / ml (0.5 pg / ml). The intra- and inter-assay variation coefficients for the determination of LPS were between 5–10%.
Todos los datos se expresan como valores medios y error típico. Se utilizó SSPS 15 para Windows (SPSS Inc., Chicago) para el análisis estadístico. Los datos fueron analizados utilizando el análisis de varianza (ANOVA) para medidas repetidas. El estadístico de contraste utilizado en el supuesto de que la esfericidad no se cumpliera era de Greenhouse-Geisser. En este análisis se estudió: All data are expressed as mean values and typical error. SSPS 15 for Windows (SPSS Inc., Chicago) was used for statistical analysis. Data were analyzed using analysis of variance (ANOVA) for repeated measures. The contrast statistic used in the assumption that the sphericity was not met was from Greenhouse-Geisser. In this analysis we studied:
- 1.one.
- El efecto del tipo de aceite ingerido, independiente del tiempo. The effect of the type of oil ingested, independent of time.
- 2.2.
- El punto de tiempo postprandial. The postprandial time point.
- 3.3.
- La interacción de ambos factores. The interaction of both factors.
Estos valores indican el grado de la respuesta postprandial en cada grupo de sujetos a cada aceite p<0,05 fue considerado significativo. These values indicate the degree of postprandial response in each group of subjects to each oil p <0.05 was considered significant.
RESULTADOS RESULTS
Los niveles de TGL postprandiales en plasma se incrementaron tras el consumo de los cuatro aceites (p <0,05), pero no se encontró ninguna diferencia entre los aceites (datos no mostrados). Postprandial plasma TGL levels increased after the consumption of the four oils (p <0.05), but no difference was found between the oils (data not shown).
Por otro lado, no se observaron cambios significativos en los niveles de CT, C-HDL y C-LDL. On the other hand, no significant changes were observed in the levels of CT, C-HDL and C-LDL.
Se determinó el contenido de compuestos fenólicos, antes y después de 20 ciclos de calentamiento a 180 °C, en los aceites que los contenían, a saber: VOO (presente de forma natural) y SOP (con compuestos fenólicos añadidos), En ambos casos los ciclos de calentamiento redujeron la cantidad de algunos de los fenoles, pero la mayoría de ellos (tirosol, apigenina, luteolina, ácido vainilínico, ácido p-cumárico, oleuropeína y oleuropeína aglicona dialdehído) todavía estaban presentes tras el calentamiento. The content of phenolic compounds was determined, before and after 20 heating cycles at 180 ° C, in the oils that contained them, namely: VOO (naturally present) and SOP (with added phenolic compounds), In both cases the heating cycles reduced the amount of some of the phenols, but most of them (tyrosol, apigenin, luteolin, vanillinic acid, p-cumaric acid, oleuropein and oleuropein aglycone dialdehyde) were still present after heating.
Ingestión aguda de los diferentes aceites de fritura y expresión de NF-kB y de IKB-a Acute ingestion of the different frying and expression oils of NF-kB and IKB-a
Con el fin de examinar si la ingestión aguda en forma de desayuno de cuatro aceites diferentes de fritura con distinto perfil lipídico y contenido de compuestos antioxidantes podría influir en la respuesta inflamatoria de las células mononucleares, los extractos nucleares de PBMCs recogidos a las 12 horas de ayuno y 4 horas después de ingerir el desayuno fueron analizados por EMSA. Los resultados mostraron que la ingesta del desayuno que contenía VOO (p = 0,029) y el desayuno con SOP (p = 0,009) disminuyó la activación de NF-kB posprandial (FIGURA 1A), aumentando la expresión de su inhibidor (FIGURA 1B), frente al resultado encontrado con los aceites carentes en compuestos fenólicos. In order to examine whether acute ingestion in the form of breakfast of four different frying oils with different lipid profile and content of antioxidant compounds could influence the inflammatory response of mononuclear cells, the nuclear extracts of PBMCs collected at 12 hours of Fasting and 4 hours after eating breakfast were analyzed by EMSA. The results showed that the intake of breakfast containing VOO (p = 0.029) and breakfast with PCOS (p = 0.009) decreased the activation of postprandial NF-kB (FIGURE 1A), increasing the expression of its inhibitor (FIGURE 1B), against the result found with the oils lacking in phenolic compounds.
Se ha estudiado si la ingesta de cuatro diferentes aceites fritos afecta la absorción de LPS endógena. Se observó una disminución significativa del nivel sérico postprandial de LPS, 2 h después de la ingesta de ambos VOO (p = 0,043) y SOP (p = 0,032) en comparación con el tiempo basal. Por el contrario, no hubo cambios significativos después del consumo de los desayunos basados en SFO y SOD (FIGURA 2). It has been studied whether the intake of four different fried oils affects the absorption of endogenous LPS. A significant decrease in the postprandial serum level of LPS was observed, 2 h after the intake of both VOO (p = 0.043) and PCOS (p = 0.032) compared to baseline time. On the contrary, there were no significant changes after breakfast consumption based on SFO and SOD (FIGURE 2).
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Claims (2)
- Categoría Category
- 56 Documentos citados Reivindicaciones afectadas 56 Documents cited Claims Affected
- X X
- ES 2288123 A1 (FURFURAL ESPAÑOL S A) 16.12.2007, todo el documento. 1-15 EN 2288123 A1 (SPANISH FURFURAL S A) 16.12.2007, the whole document. 1-15
- A TO
- 16 16
- X X
- WO 0038541 A1 (UNIELVER) 06.07.2000, reivindicaciones. 1-15 WO 0038541 A1 (UNIELVER) 06.07.2000, claims. 1-15
- A TO
- ES 2283191 A1 (ANTAS PHARMA S A) 16.10.2007, todo el documento. 1-16 EN 2283191 A1 (BEFORE PHARMA S A) 16.10.2007, the whole document. 1-16
- A TO
- EP 1221286 A1 (UNILEVER) 10.07.2002, todo el documento. 1-16 EP 1221286 A1 (UNILEVER) 10.07.2002, the whole document. 1-16
- A TO
- US 6641850 B1 (STEWART & LYNDA RESNICK TRUST) 01.11.2003, todo el documento. 1-16 US 6641850 B1 (STEWART & LYNDA RESNICK TRUST) 01.11.2003, the whole document. 1-16
- Categoría de los documentos citados X: de particular relevancia Y: de particular relevancia combinado con otro/s de la misma categoría A: refleja el estado de la técnica O: referido a divulgación no escrita P: publicado entre la fecha de prioridad y la de presentación de la solicitud E: documento anterior, pero publicado después de la fecha de presentación de la solicitud Category of the documents cited X: of particular relevance Y: of particular relevance combined with other / s of the same category A: reflects the state of the art O: refers to unwritten disclosure P: published between the priority date and the date of priority submission of the application E: previous document, but published after the date of submission of the application
- El presente informe ha sido realizado • para todas las reivindicaciones • para las reivindicaciones nº: This report has been prepared • for all claims • for claims no:
- Fecha de realización del informe 12.02.2013 Date of realization of the report 12.02.2013
- Examinador J. Manso Tomico Página 1/4 Examiner J. Manso Tomico Page 1/4
- Novedad (Art. 6.1 LP 11/1986) Novelty (Art. 6.1 LP 11/1986)
- Reivindicaciones Reivindicaciones 1-16 SI NO Claims Claims 1-16 IF NOT
- Actividad inventiva (Art. 8.1 LP11/1986) Inventive activity (Art. 8.1 LP11 / 1986)
- Reivindicaciones Reivindicaciones 16 1-15 SI NO Claims Claims 16 1-15 IF NOT
- Documento Document
- Número Publicación o Identificación Fecha Publicación Publication or Identification Number publication date
- D01 D01
- ES 2288123 A1 (FURFURAL ESPAÑOL S A) 16.12.2007 ES 2288123 A1 (SPANISH FURFURAL S A) 16.12.2007
- D02 D02
- WO 0038541 A1 (UNIELVER) 06.07.2000 WO 0038541 A1 (UNIELVER) 06.07.2000
- D03 D03
- ES 2283191 A1 (ANTAS PHARMA S A) 16.10.2007 EN 2283191 A1 (BEFORE PHARMA S A) 16.10.2007
- D04 D04
- EP 1221286 A1 (UNILEVER) 10.07.2002 EP 1221286 A1 (UNILEVER) 10.07.2002
- D05 D05
- US 6641850 B1 (STEWART & LYNDA RESNICK TRUST) 01.11.2003 US 6641850 B1 (STEWART & LYNDA RESNICK TRUST) 01.11.2003
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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ES201131058A ES2397175B1 (en) | 2011-06-22 | 2011-06-22 | Phenolic compounds of olive oil in a given concentration and its uses |
PCT/ES2012/070463 WO2012175780A1 (en) | 2011-06-22 | 2012-06-21 | Phenolic compositions of olive oil in a determined concentration and uses thereof |
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ES201131058A ES2397175B1 (en) | 2011-06-22 | 2011-06-22 | Phenolic compounds of olive oil in a given concentration and its uses |
Publications (2)
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ES2397175A1 ES2397175A1 (en) | 2013-03-05 |
ES2397175B1 true ES2397175B1 (en) | 2014-01-20 |
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ES201131058A Expired - Fee Related ES2397175B1 (en) | 2011-06-22 | 2011-06-22 | Phenolic compounds of olive oil in a given concentration and its uses |
Country Status (2)
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ES (1) | ES2397175B1 (en) |
WO (1) | WO2012175780A1 (en) |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2355778A1 (en) * | 1998-12-23 | 2000-07-06 | Unilever Plc | Fortification of food products with olive fruit ingredients |
US6641850B1 (en) * | 1999-04-19 | 2003-11-04 | Stewart And Lynda Resnick Revocable Trust | Methods of using pomegranate extracts for causing regression in lesions due to arteriosclerosis in humans |
EP1221286B1 (en) * | 2000-12-22 | 2005-01-26 | Unilever N.V. | Method for the preparation of oil having increased polyphenol content |
ES2283191B1 (en) * | 2005-09-02 | 2008-10-16 | Antas Pharma, S.A. | OLIVE PULP BIOMASS WITH HIGH CONTENT IN PHENOLIC ANTIOXIDANTS, PROCEDURE OF OBTAINING, FORMULATIONS AND USES OF THE SAME. |
ES2288123B1 (en) * | 2006-06-05 | 2008-10-01 | Furfural Español, S.A. | FUNCTIONAL FOOD COMPOSITION RICH IN PHENOLIC COMPOUNDS AND USE OF SUCH COMPOSITION. |
-
2011
- 2011-06-22 ES ES201131058A patent/ES2397175B1/en not_active Expired - Fee Related
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2012
- 2012-06-21 WO PCT/ES2012/070463 patent/WO2012175780A1/en active Application Filing
Also Published As
Publication number | Publication date |
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ES2397175A1 (en) | 2013-03-05 |
WO2012175780A1 (en) | 2012-12-27 |
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