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      Bioactive Flavonoids, Antioxidant Behaviour, and Cytoprotective Effects of Dried Grapefruit Peels ( Citrus paradisi Macf.)

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          Abstract

          Grapefruit ( Citrus paradisi Macf.) is an important cultivar of the Citrus genus which contains a number of nutrients beneficial to human health. The objective of the present study was to evaluate changes in bioactive flavonoids, antioxidant behaviour, and in vitro cytoprotective effect of processed white and pink peels after oven-drying (45°C–60°C) and freeze-drying treatments. Comparison with fresh grapefruit peels was also assessed. Significant increases in DPPH, FRAPS, and ABTS values were observed in dried grapefruit peel samples in comparison with fresh peels, indicating the suitability of the treatments for use as tools to greatly enhance the antioxidant potential of these natural byproducts. A total of thirteen flavonoids were quantified in grapefruit peel extracts by HPLC-MS/MS. It was found that naringin, followed by isonaringin, was the main flavonoid occurring in fresh, oven-dried, and freeze-dried grapefruit peels. In vivo assay revealed that fresh and oven-dried grapefruit peel extracts (45°C) exerted a strong cytoprotective effect on SH-SY5Y neuroblastoma cell lines at concentrations ranging within 0.1–0.25 mg/mL. Our data suggest that grapefruit ( Citrus paradisi Macf.) peel has considerable potential as a source of natural bioactive flavonoids with outstanding antioxidant activity which can be used as agents in several therapeutic strategies.

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          Most cited references53

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          Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration.

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            Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity.

            Significantly, much of the activity of Citrus flavonoids appears to impact blood and microvascular endothelial cells, and it is not surprising that the two main areas of research on the biological actions of Citrus flavonoids have been inflammation and cancer. Epidemiological and animal studies point to a possible protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological action are still not completely known. Many of the pharmacological properties of Citrus flavonoids can be linked to the abilities of these compounds to inhibit enzymes involved in cell activation. Attempts to control cancer involve a variety of means, including the use of suppressing, blocking, and transforming agents. Suppressing agents prevent the formation of new cancers from procarcinogens, and blocking agents prevent carcinogenic compounds from reaching critical initiation sites, while transformation agents act to facilitate the metabolism of carcinogenic components into less toxic materials or prevent their biological actions. Flavonoids can act as all three types of agent. Many epidemiological studies have shown that regular flavonoid intake is associated with a reduced risk of cardiovascular diseases. In coronary heart disease, the protective effects of flavonoids include mainly antithrombotic, anti-ischemic, anti-oxidant, and vasorelaxant. It is suggested that flavonoids decrease the risk of coronary heart disease by three major actions: improving coronary vasodilatation, decreasing the ability of platelets in the blood to clot, and preventing low-density lipoproteins (LDLs) from oxidizing. The anti-inflammatory properties of the Citrus flavonoids have also been studied. Several key studies have shown that the anti-inflammatory properties of Citrus flavonoids are due to its inhibition of the synthesis and biological activities of different pro-inflammatory mediators, mainly the arachidonic acid derivatives, prostaglandins E 2, F 2, and thromboxane A 2. The anti-oxidant and anti-inflammatory properties of Citrus flavonoids can play a key role in their activity against several degenerative diseases and particularly brain diseases. The most abundant Citrus flavonoids are flavanones, such as hesperidin, naringin, or neohesperidin. However, generally, the flavones, such as diosmin, apigenin, or luteolin, exhibit higher biological activity, even though they occur in much lower concentrations. Diosmin and rutin have a demonstrated activity as a venotonic agent and are present in several pharmaceutical products. Apigenin and their glucosides have been shown a good anti-inflammatory activity without the side effects of other anti-inflammatory products. In this paper, we discuss the relation between each structural factor of Citrus flavonoids and the anticancer, anti-inflammatory, and cardiovascular protection activity of Citrus flavonoids and their role in degenerative diseases.
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              The neuroprotective potential of flavonoids: a multiplicity of effects.

              Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi Publishing Corporation
                1942-0900
                1942-0994
                2016
                21 January 2016
                : 2016
                : 8915729
                Affiliations
                1Analytical Chemistry and Food Technology Area, Faculty of Pharmacy, University of Castilla-La Mancha, 02071 Albacete, Spain
                2Food Technology Area, Faculty of Chemistry, University of Castilla-La Mancha, 02071 Ciudad Real, Spain
                3Medical Sciences Department, Faculty of Medicine, University of Castilla-La Mancha, 02071 Albacete, Spain
                Author notes
                *Lucia Castro-Vazquez: luciaisabel.castro@ 123456uclm.es

                Academic Editor: Denis Delic

                Article
                10.1155/2016/8915729
                4745316
                26904169
                63fa114a-5fa1-4917-b641-b0bcc69ed594
                Copyright © 2016 Lucia Castro-Vazquez et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 October 2015
                : 30 November 2015
                : 1 December 2015
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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