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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">2023-5898</article-id>
      <article-id pub-id-type="doi">10.17179/excli2022-5898</article-id>
      <article-id pub-id-type="pii">Doc315</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Letter to the editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Recent studies on berberine and its biological and pharmacological activities</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Nadalin</surname>
            <given-names>Priscilla</given-names>
          </name>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kim</surname>
            <given-names>Yong-Goo</given-names>
          </name>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Park</surname>
            <given-names>Sang Un</given-names>
          </name>
          <xref ref-type="corresp" rid="COR1">&#x0002a;</xref>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
      </contrib-group>
      <aff id="A1">
        <label>1</label>Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea</aff>
      <aff id="A2">
        <label>2</label>Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, 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>28</day>
        <month>02</month>
        <year>2023</year>
      </pub-date>
      <pub-date pub-type="collection">
        <year>2023</year>
      </pub-date>
      <volume>22</volume>
      <fpage>315</fpage>
      <lpage>328</lpage>
      <history>
        <date date-type="received">
          <day>02</day>
          <month>02</month>
          <year>2023</year>
        </date>
        <date date-type="accepted">
          <day>21</day>
          <month>02</month>
          <year>2023</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Copyright &#xA9; 2023 Nadalin et al.</copyright-statement>
        <copyright-year>2023</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/vol22/excli2023-5898.pdf">This article is available from https://www.excli.de/vol22/excli2023-5898.pdf</self-uri>
    </article-meta>
  </front>
  <body>
    <sec>
      <title>⁯</title><p>Benzylisoquinoline alkaloids (BIAs) are a variety of plant chemicals that consist of roughly 2,500 known compounds. Many BIAs are characterized by potent pharmacological activities, notably the narcotic analgesics morphine and codeine, the antimicrobials sanguinarine and berberine, the muscle relaxants (&#x2B;)-tubocurarine and papaverine, and the cough suppressant and anticancer drug noscapine. A number of medicines that have been known to humankind since ancient times are plant-derived BIAs (Hagel and Facchini, 2013[<xref ref-type="bibr" rid="R26">26</xref>]).</p><p>Berberine (BBR), a yellowish crystalline benzylisoquinoline alkaloid, is an active compound found in several plants. BBR has been used in traditional Chinese medicine for a long time to treat several conditions (Zhu et al., 2022[<xref ref-type="bibr" rid="R107">107</xref>]). BBR alkaloids are found in the leaves, bark, twigs, rhizomes, roots, and stems of plants, with bark and roots containing reasonably high amounts of BBR in comparison to other plant parts (Andola et al., 2010[<xref ref-type="bibr" rid="R7">7</xref>]). BBR is a tetracyclic ring system consisting of an N-benzyltetrahydroisoquinoline core with an incorporated additional C13 carbon bridge, which is formed through an oxidative step where the N-methyl group is provided by S-adenosyl methionine to an iminium ion, with a consequent cyclization into an aromatic ring through the phenolic hydroxyl. Starting from tyrosine, BBR biosynthesis consists of 13 stages in which various enzymatic reactions are involved (Singh et al., 2021[<xref ref-type="bibr" rid="R70">70</xref>]). </p><p>BBR has been reported to be useful for a wide range of biological and pharmacological activities, including antioxidant, anti-inflammatory, anticancer, antimicrobial, antidepressant, hepatoprotective, hypolipidemic, and hypoglycemic activities (Almatroodi et al., 2022[<xref ref-type="bibr" rid="R5">5</xref>]; Behl et al., 2022[<xref ref-type="bibr" rid="R8">8</xref>]; Cheng et al., 2022[<xref ref-type="bibr" rid="R11">11</xref>]; Och et al., 2022[<xref ref-type="bibr" rid="R54">54</xref>]; Yarmohammadi et al., 2022[<xref ref-type="bibr" rid="R93">93</xref>]; Mohammadian Haftcheshmeh and Momtazi&#x2010;Borojeni, 2021[<xref ref-type="bibr" rid="R48">48</xref>]). Interestingly, many studies have provided evidence suggesting that BBR is a valuable drug candidate with a wide range of therapeutic uses (Mujtaba et al., 2022[<xref ref-type="bibr" rid="R49">49</xref>]). Here, we report a summary of the current literature available on the biological and pharmacological activities of BBR (Table 1<xref ref-type="fig" rid="T1">(Tab. 1)</xref>; References in Table 1: Abdulredha et al., 2021[<xref ref-type="bibr" rid="R1">1</xref>]; Abudureyimu et al., 2020[<xref ref-type="bibr" rid="R2">2</xref>]; Akhzari et al., 2022[<xref ref-type="bibr" rid="R3">3</xref>]; Albasher et al., 2020[<xref ref-type="bibr" rid="R4">4</xref>]; An et al., 2022[<xref ref-type="bibr" rid="R6">6</xref>]; Chen et al., 2021[<xref ref-type="bibr" rid="R10">10</xref>], 2022[<xref ref-type="bibr" rid="R9">9</xref>]; Cole et al., 2021[<xref ref-type="bibr" rid="R12">12</xref>]; Cui et al., 2022[<xref ref-type="bibr" rid="R13">13</xref>]; Dai et al., 2021[<xref ref-type="bibr" rid="R14">14</xref>], 2022[<xref ref-type="bibr" rid="R15">15</xref>]; Deng and Ma, 2021[<xref ref-type="bibr" rid="R16">16</xref>]; Deng et al., 2022[<xref ref-type="bibr" rid="R17">17</xref>]; Diao et al., 2022[<xref ref-type="bibr" rid="R18">18</xref>]; Ding et al., 2021[<xref ref-type="bibr" rid="R19">19</xref>]; Duarte-Olivenza et al., 2021[<xref ref-type="bibr" rid="R20">20</xref>]; Ehteshamfar et al., 2020[<xref ref-type="bibr" rid="R21">21</xref>]; Fang et al., 2022[<xref ref-type="bibr" rid="R22">22</xref>]; Fu et al., 2020[<xref ref-type="bibr" rid="R23">23</xref>]; Ghanem et al., 2021[<xref ref-type="bibr" rid="R24">24</xref>]; Gu et al., 2021[<xref ref-type="bibr" rid="R25">25</xref>]; Han et al., 2022[<xref ref-type="bibr" rid="R27">27</xref>]; He et al., 2021[<xref ref-type="bibr" rid="R28">28</xref>]; Huang et al., 2021[<xref ref-type="bibr" rid="R30">30</xref>], 2022[<xref ref-type="bibr" rid="R29">29</xref>]; Ibrahim Fouad and Ahmed, 2021[<xref ref-type="bibr" rid="R31">31</xref>]; Jia et al., 2022[<xref ref-type="bibr" rid="R32">32</xref>]; Jiang et al., 2021[<xref ref-type="bibr" rid="R33">33</xref>]; Kadir et al., 2022[<xref ref-type="bibr" rid="R34">34</xref>]; Kang et al., 2020[<xref ref-type="bibr" rid="R35">35</xref>]; Li et al., 2020[<xref ref-type="bibr" rid="R38">38</xref>], 2021[<xref ref-type="bibr" rid="R36">36</xref>], 2022[<xref ref-type="bibr" rid="R37">37</xref>]; Liang et al., 2021[<xref ref-type="bibr" rid="R39">39</xref>]; Liu et al., 2022[<xref ref-type="bibr" rid="R40">40</xref>]; Luo et al., 2022[<xref ref-type="bibr" rid="R41">41</xref>]; Lv et al., 2022[<xref ref-type="bibr" rid="R42">42</xref>]; Ma et al., 2021[<xref ref-type="bibr" rid="R43">43</xref>], 2022[<xref ref-type="bibr" rid="R44">44</xref>]; Malekinezhad et al., 2021[<xref ref-type="bibr" rid="R45">45</xref>]; Man et al., 2022[<xref ref-type="bibr" rid="R46">46</xref>]; Mishra et al., 2020[<xref ref-type="bibr" rid="R47">47</xref>]; Ni et al., 2022[<xref ref-type="bibr" rid="R50">50</xref>][<xref ref-type="bibr" rid="R51">51</xref>]; Noh et al., 2022[<xref ref-type="bibr" rid="R52">52</xref>]; Obchoei et al., 2022[<xref ref-type="bibr" rid="R53">53</xref>]; Pan et al., 2022[<xref ref-type="bibr" rid="R55">55</xref>]; Pang et al., 2021[<xref ref-type="bibr" rid="R56">56</xref>]; Park et al., 2022[<xref ref-type="bibr" rid="R57">57</xref>]; Pu et al., 2021[<xref ref-type="bibr" rid="R58">58</xref>]; Qiu et al., 2021[<xref ref-type="bibr" rid="R59">59</xref>]; Qu et al., 2020[<xref ref-type="bibr" rid="R60">60</xref>]; Ren et al., 2021[<xref ref-type="bibr" rid="R61">61</xref>]; Rong et al., 2022[<xref ref-type="bibr" rid="R62">62</xref>]; Seth and Chopra, 2022[<xref ref-type="bibr" rid="R64">64</xref>]; Seth et al., 2021[<xref ref-type="bibr" rid="R63">63</xref>]; Shaker et al., 2021[<xref ref-type="bibr" rid="R65">65</xref>]; Shan et al., 2021[<xref ref-type="bibr" rid="R66">66</xref>]; Shao et al., 2021[<xref ref-type="bibr" rid="R67">67</xref>]; Shen et al., 2021[<xref ref-type="bibr" rid="R68">68</xref>]; Shu et al., 2021[<xref ref-type="bibr" rid="R69">69</xref>]; Sui et al., 2021[<xref ref-type="bibr" rid="R71">71</xref>]; Sun et al., 2022[<xref ref-type="bibr" rid="R72">72</xref>]; Szalak et al., 2021[<xref ref-type="bibr" rid="R73">73</xref>]; Tang et al., 2021[<xref ref-type="bibr" rid="R74">74</xref>]; Tian et al., 2021[<xref ref-type="bibr" rid="R75">75</xref>], 2022[<xref ref-type="bibr" rid="R76">76</xref>]; Vita et al., 2021[<xref ref-type="bibr" rid="R77">77</xref>]; Waly et al., 2022[<xref ref-type="bibr" rid="R78">78</xref>]; Wang et al., 2021[<xref ref-type="bibr" rid="R80">80</xref>], 2022[<xref ref-type="bibr" rid="R79">79</xref>]; Wen et al., 2022[<xref ref-type="bibr" rid="R81">81</xref>]; Wolf et al., 2021[<xref ref-type="bibr" rid="R82">82</xref>]; Wu et al., 2021[<xref ref-type="bibr" rid="R83">83</xref>]; Xia et al., 2022[<xref ref-type="bibr" rid="R84">84</xref>]; Xiang et al., 2021[<xref ref-type="bibr" rid="R85">85</xref>]; Xie et al., 2020[<xref ref-type="bibr" rid="R86">86</xref>], 2021[<xref ref-type="bibr" rid="R88">88</xref>], 2022[<xref ref-type="bibr" rid="R87">87</xref>]; Xu et al., 2021[<xref ref-type="bibr" rid="R89">89</xref>]; Yan et al., 2022[<xref ref-type="bibr" rid="R90">90</xref>]; Yang et al., 2021[<xref ref-type="bibr" rid="R92">92</xref>], 2022[<xref ref-type="bibr" rid="R91">91</xref>]; Ye et al., 2021[<xref ref-type="bibr" rid="R94">94</xref>], 2022[<xref ref-type="bibr" rid="R95">95</xref>]; Yi et al., 2021[<xref ref-type="bibr" rid="R96">96</xref>]; Yin et al., 2021[<xref ref-type="bibr" rid="R97">97</xref>]; Yu et al., 2021[<xref ref-type="bibr" rid="R98">98</xref>]; Zhai et al., 2020[<xref ref-type="bibr" rid="R99">99</xref>][<xref ref-type="bibr" rid="R100">100</xref>]; Zhang et al., 2022[<xref ref-type="bibr" rid="R101">101</xref>][<xref ref-type="bibr" rid="R102">102</xref>]; Zhao et al., 2021[<xref ref-type="bibr" rid="R103">103</xref>]; Zheng et al., 2021[<xref ref-type="bibr" rid="R104">104</xref>][<xref ref-type="bibr" rid="R105">105</xref>]; Zhu et al., 2021[<xref ref-type="bibr" rid="R106">106</xref>]).</p></sec>
    <sec>
      <title>Notes</title><p>Priscilla Nadalin and Yong-Goo Kim contributed equally as first author.</p></sec>
    <sec>
      <title>Declaration</title><sec><title>Conflict of interest statement</title><p>The authors have no conflicts of interest to declare.</p></sec><sec><title>Acknowledgments</title><p>This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022R1I1A3054240)</p></sec></sec>
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  <floats-wrap>
    <fig id="T1" position="float">
      <label>Table 1</label>
      <caption><title>Recent studies on the biological and pharmacological activities of berberine</title></caption>
      <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="EXCLI-22-315-t-001" />
    </fig>
  </floats-wrap>
</article>