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      Anti-inflammatory properties of dietary flavonoids Translated title: Propiedades antiinflamatorias de los flavonoides de la dieta

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          Abstract

          Flavonoids are a group of natural substances that are located in sources of vegetal origin. More than 4,000 varieties of flavonoids have been identified. All of them are phenyl-benzopyrones of low molecular weight with a basic structure formed by two benzene rings united through a heterocyclic pyrane or pyrone. Besides their relevance in plants, flavonoids are important for human health. Their antioxidant capacity confers a therapeutic potential in cardiovascular diseases, gastric or duodenal ulcers, cancer or hepatic pathologies. Also important are their antiviral and anti-allergic actions, as well as their anti-thrombotic and anti-inflammatory properties. Prostaglandins and nitric oxide biosynthesis is involved in inflammation, and isoforms of inducible nitric oxide synthase (iNOS) and of cyclooxygenase (COX-2) are responsible for the production of a great amount of these mediators. It has been demonstrated that flavonoids are able to inhibit both enzymes, as well as other mediators of the inflammatory process such as reactive C protein or adhesion molecules. Modulation of the cascade of molecular events leading to the overexpression of those mediators include inhibition of transcription factors such as nuclear factor kappa B and AP-1, through the inhibition of protein kinases involved in signal transduction. Increased antioxidant defenses through activation of the NF-E2 related factor 2 (Nrf2) also contribute to the anti-inflammatory capacity of flavonoids

          Translated abstract

          Los flavonoides son un grupo de las sustancias naturales que se encuentran en fuentes de origen vegetal, existiendo más de 4.000 variedades. Todos son fenilbenzopironas de peso molecular bajo con una estructura básica formada por dos anillos heterocíclicos de benceno unidos a través de un pirano o de una pirona. Además de su función en las plantas, los flavonoides son importantes para la salud humana. Su capacidad antioxidante confiere un potencial terapéutico en enfermedades cardiovasculares, úlceras gástricas o duodenales, cáncer o patologías hepáticas. También son importantes sus acciones antivirales y antialérgicas, así como sus características antitrombóticas y antiinflamatorias. La síntesis de prostaglandinas y de óxido nítrico está implicada en la inflamación, e isoformas de la óxido nítrico sintetasa (iNOS) y de la ciclooxigenasa (COX-2) son responsables de la producción de una gran cantidad de estos mediadores. Se ha demostrado que los flavonoides pueden inhibir ambas enzimas, así como otros mediadores del proceso inflamatorio tales como la proteína C reactiva o diversas moléculas de adhesión. La modulación de la cascada de los acontecimientos moleculares que conducen al aumento en la expresión de estos mediadores incluye la inhibición de factores de transcripción tales como el factor nuclear kappaB y el factor AP-1, a través de la inhibición de diferentes proteína quinasas. Otros factores, tales como el incremento de las defensas antioxidantes a través del factor Nrf2 pueden también contribuir a las propiedades antiinflamatorias de los flavonoides

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          The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer.

          Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.
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            Flavonoids: antioxidants or signalling molecules?

            Many studies are accumulating that report the neuroprotective, cardioprotective, and chemopreventive actions of dietary flavonoids. While there has been a major focus on the antioxidant properties, there is an emerging view that flavonoids, and their in vivo metabolites, do not act as conventional hydrogen-donating antioxidants but may exert modulatory actions in cells through actions at protein kinase and lipid kinase signalling pathways. Flavonoids, and more recently their metabolites, have been reported to act at phosphoinositide 3-kinase (PI 3-kinase), Akt/protein kinase B (Akt/PKB), tyrosine kinases, protein kinase C (PKC), and mitogen activated protein kinase (MAP kinase) signalling cascades. Inhibitory or stimulatory actions at these pathways are likely to affect cellular function profoundly by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of flavonoids, either as antioxidants or modulators of cell signalling, and the influence of their metabolism on these properties are key to the evaluation of these potent biomolecules as anticancer agents, cardioprotectants, and inhibitors of neurodegeneration
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              Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury.

              Understanding the molecular pathway(s) of antioxidant gene regulation is of crucial importance for developing antioxidant-inducing agents for the intervention of oxidative cardiac disorders. Accordingly, this study was undertaken to determine the role of Nrf2 signaling in the basal expression as well as the chemical inducibility of endogenous antioxidants and phase 2 enzymes in cardiac fibroblasts. The basal expression of a scope of key cellular antioxidants and phase 2 enzymes was significantly lower in cardiac fibroblasts derived from Nrf2-/- mice than those from wild type control. These include catalase, reduced glutathione (GSH), glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). Incubation of Nrf2+/+ cardiac fibroblasts with 3H-1,2-dithiole-3-thione (D3T) led to a significant induction of superoxide dismutase (SOD), catalase, GSH, GR, glutathione peroxidase (GPx), GST, and NQO1. The inducibility of SOD, catalase, GSH, GR, GST, and NQO1, but not GPx by D3T was completely abolished in Nrf2-/- cells. The Nrf2-/- cardiac fibroblasts were much more sensitive to reactive oxygen and nitrogen species-mediated cytotoxicity. Upregulation of antioxidants and phase 2 enzymes by D3T in Nrf2+/+ cardiac fibroblasts resulted in a dramatically increased resistance to the above species-induced cytotoxicity. In contrast, D3T-treatment of the Nrf2-/- cells only provided a slight cytoprotection. Taken together, this study demonstrates for the first time that Nrf2 is critically involved in the regulation of the basal expression and chemical induction of a number of antioxidants and phase 2 enzymes in cardiac fibroblasts, and is an important factor in controlling cardiac cellular susceptibility to reactive oxygen and nitrogen species-induced cytotoxicity.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                nh
                Nutrición Hospitalaria
                Nutr. Hosp.
                Sociedad Española de Nutrición Parenteral y Enteral (Madrid )
                0212-1611
                June 2007
                : 22
                : 3
                : 287-293
                Affiliations
                [1 ] Universidad de León Spain
                Article
                S0212-16112007000400002
                8dd535dd-5abd-47e8-a401-ee5d8c79143f

                http://creativecommons.org/licenses/by/4.0/

                History
                Categories
                NUTRITION & DIETETICS

                Nutrition & Dietetics
                Flavonoids,Inflammation,Oxidative stress,Nuclear factor kappa B,Nitric oxide,Flavonoides,Inflamación,Estrés oxidativo,Factor nuclear kappa B,Òxido nítrico

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