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      Cancer chemoprevention through dietary flavonoids: what’s limiting?

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          Abstract

          Flavonoids are polyphenols that are found in numerous edible plant species. Data obtained from preclinical and clinical studies suggest that specific flavonoids are chemo-preventive and cytotoxic against various cancers via a multitude of mechanisms. However, the clinical use of flavonoids is limited due to challenges associated with their effective use, including (1) the isolation and purification of flavonoids from their natural resources; (2) demonstration of the effects of flavonoids in reducing the risk of certain cancer, in tandem with the cost and time needed for epidemiological studies, and (3) numerous pharmacokinetic challenges (e.g., bioavailability, drug–drug interactions, and metabolic instability). Currently, numerous approaches are being used to surmount some of these challenges, thereby increasing the likelihood of flavonoids being used as chemo-preventive drugs in the clinic. In this review, we summarize the most important challenges and efforts that are being made to surmount these challenges.

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          Cancer chemoprevention with dietary phytochemicals.

          Chemoprevention refers to the use of agents to inhibit, reverse or retard tumorigenesis. Numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents, but attention has recently been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals.
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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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              Interaction between phenolics and gut microbiota: role in human health.

              Dietary phenolic compounds are often transformed before absorption. This transformation modulates their biological activity. Different studies have been carried out to understand gut microbiota transformations of particular polyphenol types and identify the responsible microorganisms. Although there are potentially thousands of different phenolic compounds in the diet, they are typically transformed to a much smaller number of metabolites. The aim of this review was to discuss the current information about the microbial degradation metabolites obtained from different phenolics and their formation pathways, identifying their differences and similarities. The modulation of gut microbial population by phenolics was also reviewed in order to understand the two-way phenolic-microbiota interaction. Clostridium and Eubacterium genera, which are phylogenetically associated, are other common elements involved in the metabolism of many phenolics. The health benefits from phenolic consumption should be attributed to their bioactive metabolites and also to the modulation of the intestinal bacterial population.
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                Author and article information

                Contributors
                Haneen.amawi@rockets.utoledo.edu
                cnsratdoc@optonline.net
                +1-419-383-1913 , amit.tiwari@utoledo.edu
                Journal
                Chin J Cancer
                Chin J Cancer
                Chinese Journal of Cancer
                BioMed Central (London )
                1000-467X
                1944-446X
                19 June 2017
                19 June 2017
                2017
                : 36
                : 50
                Affiliations
                [1 ]ISNI 0000 0001 2184 944X, GRID grid.267337.4, Department of Pharmacology and Systems Therapeutics, College of Pharmacy and Pharmaceutical Sciences, , University of Toledo, ; Toledo, OH 43560 USA
                [2 ]ISNI 0000 0001 1954 7928, GRID grid.264091.8, Pharmaceutical Sciences, College of Pharmacy, , St. John’s University, ; Queens, NY 11432 USA
                [3 ]ISNI 0000 0001 2184 944X, GRID grid.267337.4, Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, , University of Toledo, ; Toledo, OH 43614 USA
                Article
                217
                10.1186/s40880-017-0217-4
                5477375
                28629389
                bf58843b-4751-477e-8003-058b653ae4df
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 3 December 2016
                : 30 May 2017
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                flavonoids,chemoprevention,silybin,silymarin,natural product drug development,pharmacokinetic challenges

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