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      The Therapeutic Potential of Apigenin

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          Abstract

          Several plant bioactive compounds have exhibited functional activities that suggest they could play a remarkable role in preventing a wide range of chronic diseases. The largest group of naturally-occurring polyphenols are the flavonoids, including apigenin. The present work is an updated overview of apigenin, focusing on its health-promoting effects/therapeutic functions and, in particular, results of in vivo research. In addition to an introduction to its chemistry, nutraceutical features have also been described. The main key findings from in vivo research, including animal models and human studies, are summarized. The beneficial indications are reported and discussed in detail, including effects in diabetes, amnesia and Alzheimer’s disease, depression and insomnia, cancer, etc. Finally, data on flavonoids from the main public databases are gathered to highlight the apigenin’s key role in dietary assessment and in the evaluation of a formulated diet, to determine exposure and to investigate its health effects in vivo.

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          Most cited references153

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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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            Apigenin: a promising molecule for cancer prevention.

            Apigenin, a naturally occurring plant flavone, abundantly present in common fruits and vegetables, is recognized as a bioactive flavonoid shown to possess anti-inflammatory, antioxidant and anticancer properties. Epidemiologic studies suggest that a diet rich in flavones is related to a decreased risk of certain cancers, particularly cancers of the breast, digestive tract, skin, prostate and certain hematological malignancies. It has been suggested that apigenin may be protective in other diseases that are affected by oxidative process, such as cardiovascular and neurological disorders, although more research needs to be conducted in this regard. Human clinical trials examining the effect of supplementation of apigenin on disease prevention have not been conducted, although there is considerable potential for apigenin to be developed as a cancer chemopreventive agent.
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              The chalcone synthase superfamily of type III polyketide synthases.

              This review covers the functionally diverse type III polyketide synthase (PKS) superfamily of plant and bacterial biosynthetic enzymes. from the discovery of chalcone synthase (CHS) in the 1970s through the end of 2001. A broader perspective is achieved by a comparison of these CHS-like enzymes to mechanistically and evolutionarily related families of enzymes, including the type I and type II PKSs, as well as the thiolases and beta-ketoacyl synthases of fatty acid metabolism. As CHS is both the most frequently occurring and best studied type III PKS, this enzyme's structure and mechanism is examined in detail. The in vivo functions and biological activities of several classes of plant natural products derived from chalcones are also discussed. Evolutionary mechanisms of type III PKS divergence are considered, as are the biological functions and activities of each of the known and functionally divergent type III PKS enzymc families (currently twelve in plants and three in bacteria). A major focus of this review is the integration of information from genetic and biochemical studies with the unique insights gained from protein X-ray crystallography and homology modeling. This structural approach has generated a number of new predictions regarding both the importance and mechanistic role of various amino acid substitutions observed among functionally diverse type III PKS enzymes.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                15 March 2019
                March 2019
                : 20
                : 6
                : 1305
                Affiliations
                [1 ]Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 44340847, Iran; bahar.salehi007@ 123456gmail.com
                [2 ]Dipartimento di Chimica, “Sapienza” Università di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy; alessandro.venditti@ 123456gmail.com
                [3 ]Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol 61663-335, Iran
                [4 ]Institute of Fermentation Technology and Microbiology, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland; dorota.kregiel@ 123456p.lodz.pl
                [5 ]Food Safety Research Center (salt), Semnan University of Medical Sciences, Semnan 35198-99951, Iran
                [6 ]CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy
                [7 ]Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy; ettore.novellino@ 123456unina.it
                [8 ]Faculty of Pharmacy of University of Coimbra Azinhaga de Santa Comba, Polo III-Saúde 3000-548 Coimbra, Portugal; ebsouto@ 123456ebsouto.pt
                [9 ]CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
                [10 ]Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA; setzerw@ 123456uah.edu
                [11 ]Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; ncmartins@ 123456med.up.pt
                [12 ]Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal
                Author notes
                [* ]Correspondence: mehdi_sharifirad@ 123456yahoo.com (M.S.-R.); javad.sharifirad@ 123456gmail.com (J.S.-R.); alessandra.durazzo@ 123456crea.gov.it (A.D.); massimo.lucarini@ 123456crea.gov.it (M.L.); asantini@ 123456unina.it (A.S.); hubert.antolak@ 123456p.lodz.pl (H.A.); elena.azzini@ 123456crea.gov.it (E.A.); Tel.: +98-543-225-1790 (M.S.-R.); +98-21-8820-0104 (J.S.-R.); +39-065-149-4439 (A.D.); +39-065-149-4446 (M.L.); +39-081-253-9317 (A.S.); +48-426-313-479 (H.A.); +39-065-149-4461 (E.A.)
                Author information
                https://orcid.org/0000-0002-6900-9797
                https://orcid.org/0000-0003-1492-6739
                https://orcid.org/0000-0002-4006-6464
                https://orcid.org/0000-0002-7301-8151
                https://orcid.org/0000-0001-5505-3327
                https://orcid.org/0000-0003-3672-4249
                https://orcid.org/0000-0002-1971-1668
                https://orcid.org/0000-0002-5934-5201
                Article
                ijms-20-01305
                10.3390/ijms20061305
                6472148
                30875872
                9f80fbd3-0f6d-4f3b-ad77-d84f44e8c27c
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 February 2019
                : 06 March 2019
                Categories
                Review

                Molecular biology
                apigenin,flavonoids,chronic diseases,diabetes,cancer
                Molecular biology
                apigenin, flavonoids, chronic diseases, diabetes, cancer

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