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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">EXCLI J</journal-id>
      <journal-title>EXCLI Journal</journal-title>
      <issn pub-type="epub">1611-2156</issn>
      <publisher>
        <publisher-name>Leibniz Research Centre for Working Environment and Human Factors</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">2021-3492</article-id>
      <article-id pub-id-type="doi">10.17179/excli2021-3492</article-id>
      <article-id pub-id-type="pii">Doc495</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Letter to the editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Flavonoids for treatment of Alzheimer&#x27;s disease: An up to date review</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Kim</surname>
            <given-names>Jae Kwang</given-names>
          </name>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Park</surname>
            <given-names>Sang Un</given-names>
          </name>
          <uri content-type="orcid">http://orcid.org//0000-0003-2157-2246</uri>
          <xref ref-type="corresp" rid="COR1">&#x0002a;</xref>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
      </contrib-group>
      <aff id="A1">
        <label>1</label>Division of Life Sciences and Bio-Resource and Environmental Center, Incheon National University, Incheon 22012, Korea</aff>
      <aff id="A2">
        <label>2</label>Department of Crop Science and Department of Smart Agriculture Systems, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea</aff>
      <author-notes>
        <corresp id="COR1">*To whom correspondence should be addressed: Sang Un Park, Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea; Tel.: +82-42-821-5730, Fax: +82-42-822-2631, E-mail: <email>supark@cnu.ac.kr</email></corresp>
      </author-notes>
      <pub-date pub-type="epub">
        <day>26</day>
        <month>02</month>
        <year>2021</year>
      </pub-date>
      <pub-date pub-type="collection">
        <year>2021</year>
      </pub-date>
      <volume>20</volume>
      <fpage>495</fpage>
      <lpage>502</lpage>
      <history>
        <date date-type="received">
          <day>07</day>
          <month>02</month>
          <year>2021</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>02</month>
          <year>2021</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Copyright &#xA9; 2021 Kim et al.</copyright-statement>
        <copyright-year>2021</copyright-year>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
          <p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/) You are free to copy, distribute and transmit the work, provided the original author and source are credited.</p>
        </license>
      </permissions>
      <self-uri xlink:href="https://www.excli.de/vol20/excli2021-3492.pdf">This article is available from https://www.excli.de/vol20/excli2021-3492.pdf</self-uri>
    </article-meta>
  </front>
  <body>
    <sec>
      <title>⁯</title><p><bold><italic>Dear Editor,</italic></bold></p><p>Flavonoids, an omnipresent class of polyphenolic compounds, are commonly present in fruits, vegetables, and plant-derived beverages (Panche et al., 2016[<xref ref-type="bibr" rid="R36">36</xref>]). To date, more than 9000 structural variants of flavonoids have been identified (Williams et al., 2004[<xref ref-type="bibr" rid="R50">50</xref>]), most of which are important pigments that impart color to flowers to attract animal pollinators. Flavonoids protect against ultraviolet radiation, organisms that cause plant diseases, and herbivores. In addition, flavonoids play a role as physiological regulators, chemical messengers, and cell cycle inhibitors (Yonekura-Sakakibara et al., 2019[<xref ref-type="bibr" rid="R54">54</xref>]). </p><p>Flavonoids are chemically composed of two aromatic ring systems (A and B rings) and a heterocyclic ring (C), forming a 15-carbon skeleton structure. This carbon structure can be abbreviated as C6-C3-C6 (Kumar and Pandey, 2013[<xref ref-type="bibr" rid="R26">26</xref>]). Based on the degree of unsaturation and substitution pattern, flavonoids can be divided into different subgroups, including anthocyanins, chalcone flavanols or catechins, flavanones, flavanonols, flavones, flavonols, and isoflavonoids (Santos-Buelga and Feliciano, 2017[<xref ref-type="bibr" rid="R38">38</xref>]).</p><p>Owing to the numerous inevitable biotic properties of flavonoids, they might act as anticancer, antioxidant, anti-inflammatory, antimicrobial, and antiviral agents. In addition, flavonoids have shown neuroprotective and cardioprotective effects in many clinical trials (Ullah et al., 2020[<xref ref-type="bibr" rid="R45">45</xref>]; Terahara, 2015[<xref ref-type="bibr" rid="R42">42</xref>]; Nijveldt et al., 2001[<xref ref-type="bibr" rid="R33">33</xref>]). Natural substances are considered to have robust protective effects against several unidentified diseases. Recently, it has been proven that they are most effective for the treatment of neurodegenerative diseases, including Alzheimer&#x27;s disease (AD). Among the different natural compounds, flavonoids are used for their neuroprotective effects. In this review, we highlight the therapeutic potential of flavonoids, especially for AD. We report the current findings on the biological and pharmacological activities of flavonoids for the treatment of AD (Table 1<xref ref-type="fig" rid="T1">(Tab. 1)</xref>; References in Table 1: Ali et al., 2018[<xref ref-type="bibr" rid="R1">1</xref>]; Ano et al., 2019[<xref ref-type="bibr" rid="R2">2</xref>]; Bao et al., 2020[<xref ref-type="bibr" rid="R3">3</xref>]; Bortolotto et al., 2020[<xref ref-type="bibr" rid="R4">4</xref>]; Chakraborty et al., 2016[<xref ref-type="bibr" rid="R5">5</xref>]; Chen et al., 2020[<xref ref-type="bibr" rid="R6">6</xref>][<xref ref-type="bibr" rid="R7">7</xref>]; Currais et al., 2018[<xref ref-type="bibr" rid="R8">8</xref>]; Daily et al., 2020[<xref ref-type="bibr" rid="R9">9</xref>]; Diaz et al., 2019[<xref ref-type="bibr" rid="R10">10</xref>]; Dourado et al., 2020[<xref ref-type="bibr" rid="R11">11</xref>]; Guo, et al., 2017[<xref ref-type="bibr" rid="R12">12</xref>]; Hajizadeh Moghaddam et al., 2020[<xref ref-type="bibr" rid="R13">13</xref>]; He et al., 2018[<xref ref-type="bibr" rid="R14">14</xref>]; Heysieattalab and Sadeghi, 2020[<xref ref-type="bibr" rid="R15">15</xref>]; Hofmann et al., 2020[<xref ref-type="bibr" rid="R16">16</xref>]; Huang et al., 2018[<xref ref-type="bibr" rid="R17">17</xref>], 2019[<xref ref-type="bibr" rid="R18">18</xref>], 2020[<xref ref-type="bibr" rid="R19">19</xref>]; Ide et al., 2018[<xref ref-type="bibr" rid="R20">20</xref>]; Iida et al., 2015[<xref ref-type="bibr" rid="R21">21</xref>]; Inoue et al., 2019[<xref ref-type="bibr" rid="R22">22</xref>]; Jin et al., 2019[<xref ref-type="bibr" rid="R23">23</xref>]; Khan et al., 2019[<xref ref-type="bibr" rid="R24">24</xref>]; Kouhestani et al., 2018[<xref ref-type="bibr" rid="R25">25</xref>]; Li et al., 2019[<xref ref-type="bibr" rid="R27">27</xref>], 2020[<xref ref-type="bibr" rid="R28">28</xref>]; Lu et al., 2018[<xref ref-type="bibr" rid="R29">29</xref>]; Masood et al., 2020[<xref ref-type="bibr" rid="R30">30</xref>]; Meng et al., 2018[<xref ref-type="bibr" rid="R31">31</xref>]; Nakagawa and Ohta, 2019[<xref ref-type="bibr" rid="R32">32</xref>]; Oladapo et al., 2021[<xref ref-type="bibr" rid="R34">34</xref>]; Pacheco et al., 2018[<xref ref-type="bibr" rid="R35">35</xref>]; Ramezani et al., 2016[<xref ref-type="bibr" rid="R37">37</xref>]; Sohanaki et al., 2016[<xref ref-type="bibr" rid="R39">39</xref>]; Soleimani Asl et al., 2019[<xref ref-type="bibr" rid="R40">40</xref>]; Sonawane et al., 2019[<xref ref-type="bibr" rid="R41">41</xref>]; Thummayot et al., 2018[<xref ref-type="bibr" rid="R43">43</xref>]; Uddin and Kabir, 2019[<xref ref-type="bibr" rid="R44">44</xref>]; Wang et al., 2015[<xref ref-type="bibr" rid="R47">47</xref>], 2016[<xref ref-type="bibr" rid="R48">48</xref>], 2017[<xref ref-type="bibr" rid="R46">46</xref>]; Wei et al., 2019[<xref ref-type="bibr" rid="R49">49</xref>]; Xia et al., 2019[<xref ref-type="bibr" rid="R51">51</xref>]; Xian et al., 2012[<xref ref-type="bibr" rid="R52">52</xref>]; Yan et al., 2019[<xref ref-type="bibr" rid="R53">53</xref>]; Yu et al., 2015[<xref ref-type="bibr" rid="R56">56</xref>], 2019[<xref ref-type="bibr" rid="R55">55</xref>]; Zhao et al., 2019[<xref ref-type="bibr" rid="R57">57</xref>]; Zhong et al., 2019[<xref ref-type="bibr" rid="R58">58</xref>]; Zhou et al., 2020[<xref ref-type="bibr" rid="R59">59</xref>]; Zhu and Wang, 2015[<xref ref-type="bibr" rid="R60">60</xref>]). </p></sec>
    <sec>
      <title>Acknowledgements</title><p>This research was supported by the Bio &#x26; Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT &#x26; Future Planning (2016M3A9A5919548).</p></sec>
    <sec>
      <title>Conflict of interest</title><p>The authors declare no conflict of interest.</p></sec>
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    </ref-list>
  </back>
  <floats-wrap>
    <fig id="T1" position="float">
      <label>Table 1</label>
      <caption><title>Pharmacological and biochemical activities of flavonoids for the treatment of Alzheimer&#x27;s disease reported recently</title></caption>
      <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="EXCLI-20-495-t-001" />
    </fig>
  </floats-wrap>
</article>