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      Intracellular signaling pathways of inflammation modulated by dietary flavonoids: The most recent evidence

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          Abstract

          Dietary flavonoids, which occur in many plant foods, are considered as the most active constituents among the plant-derived ones in vitro and in vivo. To date, many studies have addressed the anti-inflammatory activity of flavonoids. However, their considerable structural diversity and in vivo bioavailability make them able to modulate different signaling pathways. The present review attempted to summarize and highlight a broad range of inflammation-associated signaling pathways modulated by flavonoids. Finally, based on the current scientist's literature, structure-activity relationships were concluded. Dietary flavonoids have the ability to attenuate inflammation by targeting different intracellular signaling pathways triggered by NF-κB, AP-1, PPAR, Nrf2, and MAPKs. Identification of the main structural features required for the modulation of these inflammation-related pathways (hydroxylation pattern, C2=C3 double bond) have an important role to play in the development of new anti-inflammatory drugs.

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          Most cited references146

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          Flavonoids: biosynthesis, biological functions, and biotechnological applications

          Flavonoids are widely distributed secondary metabolites with different metabolic functions in plants. The elucidation of the biosynthetic pathways, as well as their regulation by MYB, basic helix-loop-helix (bHLH), and WD40-type transcription factors, has allowed metabolic engineering of plants through the manipulation of the different final products with valuable applications. The present review describes the regulation of flavonoid biosynthesis, as well as the biological functions of flavonoids in plants, such as in defense against UV-B radiation and pathogen infection, nodulation, and pollen fertility. In addition, we discuss different strategies and achievements through the genetic engineering of flavonoid biosynthesis with implication in the industry and the combinatorial biosynthesis in microorganisms by the reconstruction of the pathway to obtain high amounts of specific compounds.
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            Antioxidant and prooxidant properties of flavonoids.

            The interest in possible health benefits of flavonoids has increased owing to their potent antioxidant and free radical scavenging activities observed in vitro. Nevertheless, the antioxidant efficacy of flavonoids in vivo is less documented and their prooxidant properties have been actually described in vivo. Due to their prooxidant properties, they are able to cause oxidative damage by reacting with various biomolecules, such as lipids, proteins and DNA. Hence, the aim of this review is to discuss both the antioxidant and prooxidant effects of flavonoids. Copyright © 2011 Elsevier B.V. All rights reserved.
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              MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits.

              Excessive inflammation is becoming accepted as a critical factor in many human diseases, including inflammatory and autoimmune disorders, neurodegenerative conditions, infection, cardiovascular diseases, and cancer. Cerebral ischemia and neurodegenerative diseases are accompanied by a marked inflammatory reaction that is initiated by expression of cytokines, adhesion molecules, and other inflammatory mediators, including prostanoids and nitric oxide. This review discusses recent advances regarding the detrimental effects of inflammation, the regulation of inflammatory signalling pathways in various diseases, and the potential molecular targets for anti-inflammatory therapy. Mitogen-activated protein kinases (MAPKs) are a family of serine/threonine protein kinases that mediate fundamental biological processes and cellular responses to external stress signals. Increased activity of MAPK, in particular p38 MAPK, and their involvement in the regulation of the synthesis of inflammation mediators at the level of transcription and translation, make them potential targets for anti-inflammatory therapeutics. Inhibitors targeting p38 MAPK and JNK pathways have been developed, and preclinical data suggest that they exhibit anti-inflammatory activity. This review discusses how these novel drugs modulate the activity of the p38 MAPK and JNK signalling cascades, and exhibit anti-inflammatory effects in preclinical disease models, primarily through the inhibition of the expression of inflammatory mediators. Use of MAPK inhibitors emerges as an attractive strategy because they are capable of reducing both the synthesis of pro-inflammatory cytokines and their signalling. Moreover, many of these drugs are small molecules that can be administered orally, and initial results of clinical trials have shown clinical benefits in patients with chronic inflammatory disease.
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                Author and article information

                Journal
                Critical Reviews in Food Science and Nutrition
                Critical Reviews in Food Science and Nutrition
                Informa UK Limited
                1040-8398
                1549-7852
                September 05 2017
                November 22 2018
                September 29 2017
                November 22 2018
                : 58
                : 17
                : 2908-2924
                Affiliations
                [1 ] College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China
                [2 ] Center for Nutrition & Health, Universidad Europea del Atlantico, Santander, Spain and Dept. of Clinical Sciences, Universitr Nutrition & Health, Universidad Europea
                [3 ] Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
                [4 ] Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macau
                Article
                10.1080/10408398.2017.1345853
                cdbb3d94-74b9-46f9-997a-a5f77c33c2e7
                © 2018
                History

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