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      Kaempferol: A Key Emphasis to Its Anticancer Potential

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          Abstract

          A marked decrease in human cancers, including breast cancer, bone cancer, and cervical cancer, has been linked to the consumption of vegetable and fruit, and the corresponding chemoprotective effect has been associated with the presence of several active molecules, such as kaempferol. Kaempferol is a major flavonoid aglycone found in many natural products, such as beans, bee pollen, broccoli, cabbage, capers, cauliflower, chia seeds, chives, cumin, moringa leaves, endive, fennel, and garlic. Kaempferol displays several pharmacological properties, among them antimicrobial, anti-inflammatory, antioxidant, antitumor, cardioprotective, neuroprotective, and antidiabetic activities, and is being applied in cancer chemotherapy. Specifically, kaempferol-rich food has been linked to a decrease in the risk of developing some types of cancers, including skin, liver, and colon. The mechanisms of action include apoptosis, cell cycle arrest at the G2/M phase, downregulation of epithelial-mesenchymal transition (EMT)-related markers, and phosphoinositide 3-kinase/protein kinase B signaling pathways. In this sense, this article reviews data from experimental studies that investigated the links between kaempferol and kaempferol-rich food intake and cancer prevention. Even though growing evidence supports the use of kaempferol for cancer prevention, further preclinical and clinical investigations using kaempferol or kaempferol-rich foods are of pivotal importance before any public health recommendation or formulation using kaempferol.

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          Most cited references116

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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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            Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity.

            The metal chelating properties of flavonoids suggest that they may play a role in metal-overload diseases and in all oxidative stress conditions involving a transition metal ion. A detailed study has been made of the ability of flavonoids to chelate iron (including Fe3+) and copper ions and its dependence of structure and pH. The acid medium may be important in some pathological conditions. In addition, the ability of flavonoids to reduce iron and copper ions and their activity-structure relationships were also investigated. To fulfill these objectives, flavones (apigenin, luteolin, kaempferol, quercetin, myricetin and rutin), isoflavones (daidzein and genistein), flavanones (taxifolin, naringenin and naringin) and a flavanol (catechin) were investigated. All flavonoids studied show higher reducing capacity for copper ions than for iron ions. The flavonoids with better Fe3+ reducing activity are those with a 2,3-double bond and possessing both the catechol group in the B-ring and the 3-hydroxyl group. The copper reducing activity seems to depend largely on the number of hydroxyl groups. The chelation studies were carried out by means of ultraviolet spectroscopy and electrospray ionisation mass spectrometry. Only flavones and the flavanol catechin interact with metal ions. At pH 7.4 and pH 5.5 all flavones studied appear to chelate Cu2+ at the same site, probably between the 5-hydroxyl and the 4-oxo groups. Myricetin and quercetin, however, at pH 7.4, appear to chelate Cu2+ additionally at the ortho-catechol group, the chelating site for catechin with Cu2+ at pH 7.4. Chelation studies of Fe3+ to flavonoids were investigated only at pH 5.5. Only myricetin and quercetin interact strongly with Fe3+, complexation probably occurring again between the 5-hydroxyl and the 4-oxo groups. Their behaviour can be explained by their ability to reduce Fe3+ at pH 5.5, suggesting that flavonoids reduce Fe3+ to Fe2+ before association.
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              Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                19 June 2019
                June 2019
                : 24
                : 12
                : 2277
                Affiliations
                [1 ]University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore 54000, Pakistan; mic_1661@ 123456yahoo.com
                [2 ]Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 44340847, Iran
                [3 ]Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences, Zabol 61615-585, Iran
                [4 ]School of Exercise and Nutrition, Deakin University, Victoria 3221, Australia; tgondal@ 123456deakin.edu.au
                [5 ]Department of Food Science, Nutrition & Home Economics, Institute of Home and Food Sciences, Government College University, Faisalabad 38000, Pakistan; f.saeed@ 123456gcuf.edu.pk (F.S.); aliimran.ft@ 123456gmail.com (A.I.); umairfood1@ 123456gmail.com (M.U.A.)
                [6 ]Department of Food Science and Technology, MNS-University of Agriculture, Multan 66000, Pakistan; shahbaz.ft@ 123456mnsuam.edu.pk
                [7 ]Department of Biochemistry, Faculty of Science, University of Yaounde 1, Yaounde P.O. Box 812, Cameroon
                [8 ]Department of Pharmacy, Faculty of Chemical & Life Sciences, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan; hkdr2006@ 123456gmail.com
                [9 ]Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; sguerreiro@ 123456ipatimup.pt
                [10 ]Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal
                [11 ]Faculty of Nutrition and Food Science, University of Porto, 4200-465 Porto, Portugal
                [12 ]Department of Biology and Biotechnology, School of Agriculture of the Polytechnic Institute of Bragança (ESA-IPB), Campus de Santa Apolónia, 5301-854 Bragança, Portugal
                [13 ]CIMO, Mountain Research Center, Polytechnic Institute of Bragança. Campus Santa Apolónia, 5301-855 Bragança, Portugal
                Author notes
                [* ]Correspondence: bahar.salehi007@ 123456gmail.com (B.S.); javad.sharifirad@ 123456gmail.com (J.S.-R.); ptsouh@ 123456gmail.com (P.V.T.F.); ncmartins@ 123456med.up.pt (N.M.); leticia@ 123456ipb.pt (L.M.E.); Tel.: +98-21-8877-7539 (B.S.); +98-21-88200104 (J.S.-R.); +23-767-662-0503 (P.V.T.F.); +351-22-5512100 (N.M.); +351-273303342 (L.M.E.)
                Author information
                https://orcid.org/0000-0002-6900-9797
                https://orcid.org/0000-0002-7301-8151
                https://orcid.org/0000-0003-3724-3527
                https://orcid.org/0000-0003-1032-6250
                https://orcid.org/0000-0002-1736-4404
                https://orcid.org/0000-0002-5934-5201
                Article
                molecules-24-02277
                10.3390/molecules24122277
                6631472
                31248102
                9e7ea439-6d8e-4fa6-a4e6-71a6c230dceb
                © 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
                : 16 April 2019
                : 15 June 2019
                Categories
                Review

                kaempferol,pharmacokinetics,pharmacodynamics,antioxidant,anticancer,chemoprevention,apoptosis,cell cycle arrest,metastasis,reactive oxygen species

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