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      Flavonoids and Related Members of the Aromatic Polyketide Group in Human Health and Disease: Do They Really Work?

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          Abstract

          Some aromatic polyketides such as dietary flavonoids have gained reputation as miraculous molecules with preeminent beneficial effects on human health, for example, as antioxidants. However, there is little conclusive evidence that dietary flavonoids provide significant leads for developing more effective drugs, as the majority appears to be of negligible medicinal importance. Some aromatic polyketides of limited distribution have shown more interesting medicinal properties and additional research should be focused on them. Combretastatins, analogues of phenoxodiol, hepatoactive kavalactones, and silymarin are showing a considerable promise in the advanced phases of clinical trials for the treatment of various pathologies. If their limitations such as adverse side effects, poor water solubility, and oral inactivity are successfully eliminated, they might be prime candidates for the development of more effective and in some case safer drugs. This review highlights some of the newer compounds, where they are in the new drug pipeline and how researchers are searching for additional likely candidates.

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          Most cited references132

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          A review on the dietary flavonoid kaempferol.

          Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.
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            Chemistry: Chemical con artists foil drug discovery.

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              Exploring the temperature-stress metabolome of Arabidopsis.

              Metabolic profiling analyses were performed to determine metabolite temporal dynamics associated with the induction of acquired thermotolerance in response to heat shock and acquired freezing tolerance in response to cold shock. Low-M(r) polar metabolite analyses were performed using gas chromatography-mass spectrometry. Eighty-one identified metabolites and 416 unidentified mass spectral tags, characterized by retention time indices and specific mass fragments, were monitored. Cold shock influenced metabolism far more profoundly than heat shock. The steady-state pool sizes of 143 and 311 metabolites or mass spectral tags were altered in response to heat and cold shock, respectively. Comparison of heat- and cold-shock response patterns revealed that the majority of heat-shock responses were shared with cold-shock responses, a previously unknown relationship. Coordinate increases in the pool sizes of amino acids derived from pyruvate and oxaloacetate, polyamine precursors, and compatible solutes were observed during both heat and cold shock. In addition, many of the metabolites that showed increases in response to both heat and cold shock in this study were previously unlinked with temperature stress. This investigation provides new insight into the mechanisms of plant adaptation to thermal stress at the metabolite level, reveals relationships between heat- and cold-shock responses, and highlights the roles of known signaling molecules and protectants.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                24 August 2020
                September 2020
                : 25
                : 17
                : 3846
                Affiliations
                [1 ]Department of Food Science, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, Kamýcká 129, Praha 6, 165 00 Praha, Czech Republic
                [2 ]Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, Prague 6, 166 28 Prague, Czech Republic; lukas.huml@ 123456vscht.cz (L.H.); michal.jurasek@ 123456gmail.com (M.J.)
                [3 ]Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technická 3, Prague 6, 166 28 Prague, Czech Republic; silvie.rimpelova@ 123456vscht.cz
                Author notes
                [* ]Correspondence: tauchen@ 123456af.czu.cz ; Tel.: +420-224-862-891
                Author information
                https://orcid.org/0000-0002-3008-1396
                Article
                molecules-25-03846
                10.3390/molecules25173846
                7504053
                32847100
                defcc50e-03e6-4d27-977d-547c67e66c89
                © 2020 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
                : 15 July 2020
                : 21 August 2020
                Categories
                Review

                flavonoids,polyketides,antioxidants,anticancer,clinical significance,dietary supplements,nutrition

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