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<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Pharmacol.</journal-id>
<journal-title>Frontiers in Pharmacology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Pharmacol.</abbrev-journal-title>
<issn pub-type="epub">1663-9812</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">816029</article-id>
<article-id pub-id-type="doi">10.3389/fphar.2022.816029</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Pharmacology</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Ethnobotanical Survey on Bitter Tea in Taiwan</article-title>
<alt-title alt-title-type="left-running-head">Chao et&#x20;al.</alt-title>
<alt-title alt-title-type="right-running-head">Survey on Taiwanese Bitter Tea</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Chao</surname>
<given-names>Jung</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="fn" rid="fn1">
<sup>&#x2020;</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/533590/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Ting-Yang</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="fn" rid="fn1">
<sup>&#x2020;</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1298440/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pao</surname>
<given-names>Li-Heng</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/939021/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Deng</surname>
<given-names>Jeng-Shyan</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cheng</surname>
<given-names>Yung-Chi</given-names>
</name>
<xref ref-type="aff" rid="aff6">
<sup>6</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/176067/overview"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Su</surname>
<given-names>Shan-Yu</given-names>
</name>
<xref ref-type="aff" rid="aff7">
<sup>7</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1013663/overview"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Huang</surname>
<given-names>Shyh-Shyun</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
<xref ref-type="aff" rid="aff8">
<sup>8</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1395910/overview"/>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Chinese Medicine Research Center</institution>, <institution>Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources</institution>, <institution>Master Program for Food and Drug Safety</institution>, <institution>China Medical University</institution>, <addr-line>Taichung</addr-line>, <country>Taiwan</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Chinese Medicine Research Center</institution>, <institution>Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources</institution>, <institution>China Medical University</institution>, <addr-line>Taichung</addr-line>, <country>Taiwan</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Graduate Institute of Health Industry Technology</institution>, <institution>Research Center for Food and Cosmetic Safety</institution>, <institution>and Research Center for Chinese Herbal Medicine</institution>, <institution>College of Human Ecology</institution>, <institution>Chang Gung University of Science and Technology</institution>, <addr-line>Taoyuan</addr-line>, <country>Taiwan</country>
</aff>
<aff id="aff4">
<sup>4</sup>
<institution>Department of Gastroenterology and Hepatology</institution>, <institution>Chang Gung Memorial Hospital</institution>, <addr-line>Taoyuan</addr-line>, <country>Taiwan</country>
</aff>
<aff id="aff5">
<sup>5</sup>
<institution>Department of Food Nutrition and Health Biotechnology</institution>, <institution>Asia University</institution>, <addr-line>Taichung</addr-line>, <country>Taiwan</country>
</aff>
<aff id="aff6">
<sup>6</sup>
<institution>Department of Pharmacology</institution>, <institution>Yale University School of Medicine</institution>, <addr-line>New Haven</addr-line>, <addr-line>CT</addr-line>, <country>United&#x20;States</country>
</aff>
<aff id="aff7">
<sup>7</sup>
<institution>Department of Chinese Medicine</institution>, <institution>China Medical University Hospital</institution>, <institution>School of Post-Baccalaureate Chinese Medicine</institution>, <institution>College of Chinese Medicine</institution>, <institution>China Medical University</institution>, <addr-line>Taichung</addr-line>, <country>Taiwan</country>
</aff>
<aff id="aff8">
<sup>8</sup>
<institution>School of Pharmacy</institution>, <institution>China Medical University</institution>, <addr-line>Taichung</addr-line>, <country>Taiwan</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>
<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/15167/overview">Michael Heinrich</ext-link>, University College London, United&#x20;Kingdom</p>
</fn>
<fn fn-type="edited-by">
<p>
<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/990900/overview">Manuel Pardo de Santayana</ext-link>, Autonomous University of Madrid, Spain</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/633715/overview">Diego Rivera</ext-link>, University of Murcia, Spain</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/882493/overview">Lukasz Luczaj</ext-link>, University of Rzeszow, Poland</p>
</fn>
<corresp id="c001">&#x2a;Correspondence: Shan-Yu Su, <email>shanyusu@gmail.com</email>; Shyh-Shyun Huang, <email>sshuang@mail.cmu.edu.tw</email>
</corresp>
<fn fn-type="equal" id="fn1">
<label>
<sup>&#x2020;</sup>
</label>
<p>These authors have contributed equally to this&#x20;work</p>
</fn>
<fn fn-type="other">
<p>This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>18</day>
<month>02</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="collection">
<year>2022</year>
</pub-date>
<volume>13</volume>
<elocation-id>816029</elocation-id>
<history>
<date date-type="received">
<day>16</day>
<month>11</month>
<year>2021</year>
</date>
<date date-type="accepted">
<day>13</day>
<month>01</month>
<year>2022</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2022 Chao, Chen, Pao, Deng, Cheng, Su and Huang.</copyright-statement>
<copyright-year>2022</copyright-year>
<copyright-holder>Chao, Chen, Pao, Deng, Cheng, Su and Huang</copyright-holder>
<license 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 License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these&#x20;terms.</p>
</license>
</permissions>
<abstract>
<p>
<bold>Ethnopharmacological evidence:</bold> In Taiwan, herbal tea is considered a traditional medicine and has been consumed for hundreds of years. In contrast to regular tea, herbal teas are prepared using plants other than the regular tea plant, Camellia sinensis (L.) Kuntze. Bitter tea (k&#x1d4;-ch&#xe1;), a series of herbal teas prepared in response to common diseases in Taiwan, is often made from local Taiwanese plants. However, the raw materials and formulations have been kept secret and verbally passed down by store owners across generations without a fixed recipe, and the constituent plant materials have not been disclosed.</p>
<p>
<bold>Aim of the study:</bold> The aim was to determine the herbal composition of bitter tea sold in Taiwan, which can facilitate further studies on pharmacological applications and conserve cultural resources.</p>
<p>
<bold>Materials and methods:</bold> Interviews were conducted through a semi-structured questionnaire. The surveyed respondents were traditional sellers of traditional herbal tea. The relevant literature was collated for a systematic analysis of the composition, characteristics, and traditional and modern applications of the plant materials used in bitter tea. We also conducted an association analysis of the composition of Taiwanese bitter tea with green herb tea (qing-cao-cha tea), another commonly consumed herbal tea in Taiwan, as well as herbal teas in neighboring areas outside Taiwan.</p>
<p>
<bold>Results:</bold> After visiting a total of 59 stores, we identified 32 bitter tea formulations and 73 plant materials. Asteraceae was the most commonly used family, and most stores used whole plants. According to a network analysis of nine plant materials used in high frequency as drug pairs, Tithonia diversifolia and Ajuga nipponensis were found to be the core plant materials used in Taiwanese bitter&#x20;tea.</p>
<p>
<bold>Conclusion:</bold> Plant materials used in Taiwanese bitter tea were distinct, with multiple therapeutic functions. Further research is required to clarify their efficacy and mechanisms.</p>
</abstract>
<kwd-group>
<kwd>Taiwanese bitter tea</kwd>
<kwd>field survey</kwd>
<kwd>Taiwanese traditional medicine</kwd>
<kwd>ethnobotany</kwd>
<kwd>health geography</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec id="s1">
<title>Introduction</title>
<p>Herbal tea is a drink composed of plants other than <italic>Camellia sinensis</italic> (L.) Kuntze of the Theaceae family&#x2014;in contrast to regular tea&#x2014;and is prepared by decocting or brewing with hot water. Herbal tea is commonly prepared with local plants that can be easily obtained (<xref ref-type="bibr" rid="B53">Fu et&#x20;al., 2018</xref>). The custom of brewing tea with herbs is found all over the world, including Europe (<xref ref-type="bibr" rid="B165">Soukand and Kalle, 2013</xref>; <xref ref-type="bibr" rid="B166">Soukand et&#x20;al., 2013</xref>), America (<xref ref-type="bibr" rid="B83">Joubert et&#x20;al., 2008</xref>), Africa (<xref ref-type="bibr" rid="B153">Roulette et&#x20;al., 2018</xref>), and Asia (<xref ref-type="bibr" rid="B71">Hu, 2005</xref>). The herbs used could be a single herb or a mixture of multiple plants. In many areas, herbal teas are used as therapeutic vehicles to treat associated health conditions (<xref ref-type="bibr" rid="B146">Poswal et&#x20;al., 2019</xref>).</p>
<p>In China, herbal tea has been consumed for more than 2000&#xa0;years (<xref ref-type="bibr" rid="B108">Liu et&#x20;al., 2013</xref>). Famous herbal teas in pan-China include those are drunk in Yao area (<xref ref-type="bibr" rid="B81">Jin et&#x20;al., 2018</xref>), Lingnan (<xref ref-type="bibr" rid="B111">Liu Y. et&#x20;al., 2013</xref>), Chaoshan (<xref ref-type="bibr" rid="B96">Li et&#x20;al., 2017</xref>), and Fujian (<xref ref-type="bibr" rid="B104">Lin, 2014</xref>), and Taiwan (<xref ref-type="bibr" rid="B27">Chang, 2005</xref>). Furthermore, this beverage has been closely associated with the prevention and treatment of local common ailments (<xref ref-type="bibr" rid="B96">Li et&#x20;al., 2017</xref>; <xref ref-type="bibr" rid="B173">Tan et&#x20;al., 2017</xref>). The herbal teas in Lingnan (<xref ref-type="bibr" rid="B111">Liu Y. et&#x20;al., 2013</xref>), Chaoshan (<xref ref-type="bibr" rid="B96">Li et&#x20;al., 2017</xref>), and Fujian (<xref ref-type="bibr" rid="B104">Lin, 2014</xref>) are called the&#x201c;cool tea,&#x201d; implying that the herbal teas are used against the hot weather in southern China. The type of herbal tea is also influenced by the traditional culture of various regions, thereby reflecting local characteristics (<xref ref-type="bibr" rid="B71">Hu, 2005</xref>).</p>
<p>Although the folk plants in Taiwan are widely used in religious rites, bathing, cuisine, and herbal tea, international literature on Taiwanese folk plants is limited. According to previous surveys, there are 1,217 wild or cultivated folk plants with medicinal purposes have been documented in Taiwan (<xref ref-type="bibr" rid="B128">Ministry of Health and Welfare, 2021</xref>). The two main herbal teas in Taiwan, bitter tea (k&#x16d;-ch&#xe1;) and green herb tea (q&#x12b;ng-c&#x103;o-ch&#xe1;), are the two most complicated applications of folk plants in Taiwan. Both of them are usually made by cooking a mixture of medicinal plants (<xref ref-type="bibr" rid="B26">Chang, 2004</xref>). The mixtures of medicinal plants, in which there are the mixtures of bioactive compounds, exert synergistic therapeutic effects (<xref ref-type="bibr" rid="B55">Gertsch, 2011</xref>; <xref ref-type="bibr" rid="B56">Gras et&#x20;al., 2018</xref>). Herbal teas in Taiwan are believed to have originated in southern China. After arriving in Taiwan, the ingredients of original herbal teas gradually turned into readily available Taiwanese native plants, and then, herbal teas that are suitable for local people were gradually developed (<xref ref-type="bibr" rid="B32">Chen and Lin, 2012</xref>).</p>
<p>Although the formulations of bitter tea and green herb tea vary across Taiwanese stores, they are all primarily advertised as having the capacity to &#x201c;clear heat&#x201d; (<xref ref-type="bibr" rid="B75">Huang et&#x20;al., 2020</xref>). In the principle of traditional Chinese medicine formulation, one to three medicinal materials play the role of core medicinal materials in an herbal mixture. Other medicinal materials are added to enhance the therapeutic effects, improve the taste, or reduce the side effects of the core plant medicinal materials (<xref ref-type="bibr" rid="B228">Zhou et&#x20;al., 2016</xref>).</p>
<p>According to previous research and surveys, the main components of green herb tea in Taiwan are <italic>Platostoma palustre</italic> (Blume) A.J.Paton, <italic>Bidens pilosa</italic> L., <italic>Pteris multifida</italic> Poir., <italic>Mentha arvensis</italic> L., <italic>Sphagneticola calendulacea</italic> (L.) Pruski, and <italic>Rhinacanthus nasutus</italic> (L.) Kurz (Huang et&#x20;al., 2020). These tea beverages prepared by mixing and decocting these plants have a refreshing, half bitter/half sweet taste, and are used for quenching thirst and relieving summer heat (Huang et&#x20;al., 2020). The other Taiwanese main herbal tea, the Taiwanese bitter tea, is also known as liver nourishing tea (y&#x103;ng-g&#x101;n-ch&#xe1;), and thick green herb tea (n&#xf3;ng-h&#xf3;u-q&#x12b;ng-c&#x103;o-ch&#xe1;). It is characterized by a bitter-dominated taste that is stronger than that of regular green herb tea (<xref ref-type="bibr" rid="B27">Chang, 2005</xref>). Although bitter tea has been consumed for hundreds of years in Taiwan, its components and core medicinal materials have not been comprehensively studied, which has impeded the investigation of its efficacy against various health conditions.</p>
<p>Traditional Chinese medicine categorizes medicinal materials according to their property and flavor. The property includes hot, warm, neutral, cool, cold. Hot and warm materials are usually taken to supply energy to the body, while cool and cold materials are taken to drain away the heat from the body (<xref ref-type="bibr" rid="B107">Liu et&#x20;al., 2020</xref>). The flavors are divided into sour, bitter, sweet, spicy, salty, and plain. Flavor is the taste of herbs in the mouth. Each of the flavors has distinct medicinal therapeutic functions. Sour herbs astringe the leakage of fluids and energy; sweet herbs tonify and harmonize; spicy herbs disperse and move; salty herbs soften and purge; plain herbs leech out dampness; and finally, the traditional therapeutic function associated with bitter herbs is heat clearing and removing dampmess (<xref ref-type="bibr" rid="B230">Bensky et&#x20;al., 2004</xref>; <xref ref-type="bibr" rid="B112">Lu et&#x20;al., 2018</xref>; Liu et&#x20;al.,. 2020). The heat-clearing and dampess-draining effects provided by the bitter taste are used to combat the discomfort caused by the summer rainy season (<xref ref-type="bibr" rid="B203">Wu, 2005</xref>). Moreover, according to a previous study, the administration of bitter drugs can help treat liver disease (<xref ref-type="bibr" rid="B184">Tsai et&#x20;al., 2020</xref>). For example, <italic>Gentiana scabra</italic> Bunge, <italic>Artemisia capillaris</italic> Thunb., and <italic>Scutellaria baicalensis</italic> Georgi are the most classical and commonly used traditional Chinese medicines for liver disease (<xref ref-type="bibr" rid="B184">Tsai et&#x20;al., 2020</xref>).</p>
<p>Only one of the two main types of herbal tea in Taiwan, the composition and pharmacology of green herb tea constituents have been studied and reported (Huang et&#x20;al., 2020), whereas those of the raw materials of bitter tea have not yet been elucidated. According to local reference books, most raw materials used in such herbal teas are either cultivated locally or wildly harvested. They require simple process after collection and are decocted after drying (<xref ref-type="bibr" rid="B27">Chang, 2005</xref>). However, the formula of Taiwanese bitter tea is not in the public domain, considering that every store keeps their recipe a secret. In the present study, we surveyed sellers of folk herbal medicine in Taiwan. The survey was conducted via interviews using semi-structured questionnaires, and information recorded included the current status of the bitter tea market in Taiwan as well as the ingredients and formulations used. The results of the present study can help reveal the ethnopharmacological aspects of bitter tea consumed in Taiwan and facilitate the conservation of such unique cultural resources.</p>
</sec>
<sec sec-type="materials|methods" id="s2">
<title>Materials and Methods</title>
<sec id="s2-1">
<title>Survey Area and Period</title>
<p>Taiwan, an island in East Asia, is located at 21&#xb0;45&#x2032;-25&#xb0;56&#x2032;N and 119&#xb0;18&#x2032;-124&#xb0;34&#x2032;E. It spans the Tropic of Cancer, covers an area of 36,197&#xa0;km<sup>2</sup>, and mostly has a subtropical climate with monsoons, warm and humid summers, and heavy rainfall. In the present study, 59 stores were visited, 25 of which provided information on bitter tea formulations and participated in the interviews. Seven stores only provided information on the bitter tea formula used in their stores but did not give interviews. The 32 sampled stores were distributed all over Taiwan (<xref ref-type="fig" rid="F1">Figure&#x20;1</xref>). The survey period was from December 2018 to April 2019, and the entire research activity was reviewed and approved by Taiwan&#x2019;s Central Regional Research Ethics Center (CRREC-107-019) (<xref ref-type="sec" rid="s12">Supplementary Figure&#x20;S1</xref>).</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>Geographical distribution of 32 stores with available bitter tea formulations. Red dots indicate that the store provided bitter tea formulation but did not receive interviews (seven stores), and green dots indicate that the store provided complete bitter tea formulation and accepted interviews (25 stores).</p>
</caption>
<graphic xlink:href="fphar-13-816029-g001.tif"/>
</fig>
</sec>
<sec id="s2-2">
<title>Interviews and Data Collection</title>
<p>A semi-structured questionnaire was used for interviews, and the subjects were store owners selling bitter tea. The stores were found online or introduced to us by organizations involved with local medicinal plants. The store owners were invited to participate in the survey, and interviews were conducted on a voluntary basis. With the permission of the informants, written records, audio recordings, and photographs were obtained, and herbal medicines were acquired by the authors. The medicinal materials were then identified using the five senses identification method, with which the expert identify the origin of medicinal materials by touch, taste, smell, hearing, and visual observation, without any equipments (<xref ref-type="bibr" rid="B69">Hsieh et&#x20;al., 2017</xref>). The specimens of the medicinal materials have been deposited in the herbarium at School of Pharmacy of China Medical University (CMU) in Taichung City, Taiwan.</p>
<p>The information collected by the interviews was divided into two parts. The first part included basic information on the store, including age and sex of the store owner, store location, and how long the store has been in operation. The second part was a semi-structured questionnaire consisting of the following questions: 1) what is the composition of bitter tea; 2) what is the traditional therapeutic indication of the bitter tea sold in your store; 3) how was the traditional knowledge of the bitter tea obtained; and 4) does the store sell dry or fresh raw materials needed to make the&#x20;tea?</p>
</sec>
<sec id="s2-3">
<title>Data Collection of Bitter Tea Plant Materials in Taiwan</title>
<p>All data on the surveyed plant materials were collated, which included the following:<list list-type="simple">
<list-item>
<p>(1) Name, including scientific name, family name, and local name. The scientific and family names of plants are presented according to the Plant List nomenclature (<xref ref-type="bibr" rid="B178">The Royal Botanic Gardens, 2013</xref>) and the Plants of the World Online (<xref ref-type="bibr" rid="B231">Royal Botanic Garden, 2021</xref>).</p>
</list-item>
<list-item>
<p>(2) Part of the plant used. This was determined by identifying the raw plant materials.</p>
</list-item>
<list-item>
<p>(3) Frequency and use value (UV). Frequency refers to the number of stores using the plant material in the survey, and UV refers to the number of stores using the plant material/total number of stores in the survey as follows (<xref ref-type="bibr" rid="B53">Fu et&#x20;al., 2018</xref>):</p>
</list-item>
</list>
<disp-formula id="equ1">
<mml:math id="m1">
<mml:mrow>
<mml:mtext>UV</mml:mtext>
<mml:mo>&#x3d;</mml:mo>
<mml:mfrac>
<mml:mrow>
<mml:mstyle displaystyle="true">
<mml:mo>&#x2211;</mml:mo>
<mml:mrow>
<mml:mtext>Ui</mml:mtext>
</mml:mrow>
</mml:mstyle>
</mml:mrow>
<mml:mi mathvariant="normal">N</mml:mi>
</mml:mfrac>
</mml:mrow>
</mml:math>
</disp-formula>Where Ui represents the individual number of the <italic>i</italic>th medicinal material, and N represents the total number of bitter tea formulations.<list list-type="simple">
<list-item>
<p>(4) Traditional therapeutic functions. This information was obtained from the Committee on <xref ref-type="bibr" rid="B176">Chinese Medicine and Pharmacy (2003)</xref> and the second edition of The Committee on <xref ref-type="bibr" rid="B177">Chinese Medicine and Pharmacy (2011)</xref>.</p>
</list-item>
<list-item>
<p>(5) The diversity of the medicinal plants was evaluated using Shannon diversity index (<xref ref-type="bibr" rid="B56">Gras et&#x20;al., 2018</xref>), which was calculated as follows:</p>
</list-item>
</list>
<disp-formula id="equ2">
<mml:math id="m2">
<mml:mrow>
<mml:mtext>Shannon&#xa0;diversity&#xa0;index</mml:mtext>
<mml:mo>&#x3d;</mml:mo>
<mml:mo>&#x2212;</mml:mo>
<mml:munderover>
<mml:mstyle displaystyle="true">
<mml:mo>&#x2211;</mml:mo>
</mml:mstyle>
<mml:mrow>
<mml:mi>i</mml:mi>
<mml:mo>&#x3d;</mml:mo>
<mml:mn>1</mml:mn>
</mml:mrow>
<mml:mi>n</mml:mi>
</mml:munderover>
<mml:mi>P</mml:mi>
<mml:mi>i</mml:mi>
<mml:mo>&#x2217;</mml:mo>
<mml:mi>l</mml:mi>
<mml:mi>o</mml:mi>
<mml:msub>
<mml:mi>g</mml:mi>
<mml:mn>2</mml:mn>
</mml:msub>
<mml:mi>P</mml:mi>
<mml:mi>i</mml:mi>
</mml:mrow>
</mml:math>
</disp-formula>Where <italic>Pi</italic> represents the proportion of the individual number of the <italic>i</italic>th medicinal material to the individual number of the total medicinal material. For example, <italic>Andrographis paniculata</italic> was used in 10 of the formulations, and the total number of individual of all species in this survey is 183. Then the <italic>Pi</italic> for <italic>Andrographis paniculata</italic> was obtained by dividing 10 by 183. Then the <inline-formula id="inf1">
<mml:math id="m3">
<mml:mrow>
<mml:mo>"</mml:mo>
<mml:mi>P</mml:mi>
<mml:mi>i</mml:mi>
<mml:mo>&#x2217;</mml:mo>
<mml:mi>l</mml:mi>
<mml:mi>o</mml:mi>
<mml:msub>
<mml:mi>g</mml:mi>
<mml:mn>2</mml:mn>
</mml:msub>
<mml:mi>P</mml:mi>
<mml:mi>i</mml:mi>
<mml:mo>"</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> for all the medicinal materials in the survey were summed up to get the Shannon diversity index.<list list-type="simple">
<list-item>
<p>(6) Modern pharmacology. Information was obtained by searching for the plant materials in the literature using the PubMed database<xref ref-type="fn" rid="fn2">
<sup>1</sup>
</xref>. Those cited in studies published before April 2021 and at a frequency greater than nine were included.</p>
</list-item>
<list-item>
<p>(7) Comparison between Taiwanese bitter tea and Taiwanese green herb tea. Based on the findings of Huang et&#x20;al. (2020), we analyzed the similarities and differences between the plant materials used for each tea and further compared differences in flavor, UV, and application in modern pharmacology.</p>
</list-item>
<list-item>
<p>(8) Comparison of herbal tea composition across three regions in southern China. By referring to relevant published articles (Liu et&#x20;al., 2013; <xref ref-type="bibr" rid="B104">Lin, 2014</xref>; <xref ref-type="bibr" rid="B96">Li et&#x20;al., 2017</xref>), a Venn diagram was plotted using an online tool<xref ref-type="fn" rid="fn3">
<sup>2</sup>
</xref> to analyze the relationships between Taiwanese bitter tea and herbal tea from Lingnan, Chaoshan, and Fujian.</p>
</list-item>
</list>
</p>
</sec>
<sec id="s2-4">
<title>Core Network Analysis of Bitter Tea Use in Taiwan</title>
<p>Core network analysis was carried out using the Traditional Chinese Medicine Inheritance Support System (TCMISS) v2.5 (<xref ref-type="bibr" rid="B202">Wu et&#x20;al., 2019</xref>; <xref ref-type="bibr" rid="B28">Chao et&#x20;al., 2020</xref>; <xref ref-type="bibr" rid="B210">Wu Z. et&#x20;al., 2020</xref>). Several matching frequency conditions were input into the software to find a suitable network diagram. Establishing connections when combinations of plant materials had a matching frequency greater than four was found the most proper to generate the network that clearly present the core medicinal materials. The length of the connection indicates the degree of matching frequency, and the size of the circles represent the relative&#x20;UV.</p>
</sec>
</sec>
<sec sec-type="results" id="s3">
<title>Results</title>
<sec id="s3-1">
<title>Respondents&#x2019; Data and Store Information</title>
<p>A total of 59 stores selling bitter tea were visited for this study. Among them, 25 participated in interviews and provided the formulations for bitter tea; 7 were unwilling to participate in the interviews but provided bitter tea formulations; and 27 declined to participate in interviews and did not provide formulations. Of the 25 traditional stores that participated in interviews, 50% have been operating for more than 50&#xa0;years. The store owners were mainly male (76%), with ages ranging from 31 to 70&#xa0;years. Knowledge on bitter tea formulations was mostly passed down through family members (76%) or apprentices (20%). All stores sold prepared bitter tea drinks (100%), 36% sold dry raw materials, and 48% sold both dry and fresh raw materials (<xref ref-type="sec" rid="s12">Supplementary Figure S2</xref>). In addition, all bitter tea sellers sold green herb&#x20;tea.</p>
</sec>
<sec id="s3-2">
<title>Plant Materials Used in Bitter Tea and Their Territories in Taiwan</title>
<p>In the present study, 73 plant materials from 72 plants belonging to 33 families and 67 genera were identified. Among the 73 medicinal materials, 60% of them were cultivated, 63% of them can be collected in the wild, and 37% were both cultivated and wild (<xref ref-type="sec" rid="s12">Supplementary Table S1</xref>). The average number of plants materials in a formulation is 5.7 (<xref ref-type="sec" rid="s12">Supplementary Table S2</xref>). The top five ranking species include <italic>Andrographis paniculata</italic> (Burm. f.) Nees, <italic>Tithonia diversifolia</italic> (Hemsl.) A. Gray (both UV &#x3d; 0.312), <italic>Ajuga nipponensis</italic> Makino, <italic>Ixeris chinensis</italic> (Thunb. ex Thunb.) Nakai (both UV &#x3d; 0.281), and <italic>Ilex asprella</italic> (Hook. &#x26; Arn.) Champ. ex Benth (UV &#x3d; 0.25). Regarding the plant families, Asteraceae was the most frequently used, comprising 16.7% among 72 plants and 75.0% among 32 formulations, followed by Lamiaceae, comprising 15.3% among total plants and 65% among formulations (<xref ref-type="fig" rid="F2">Figure&#x20;2A</xref>). The most used plant parts were the whole plant (41.1%), followed by the root and rhizome (20.6%) (<xref ref-type="fig" rid="F2">Figure&#x20;2B</xref>).</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>Origin analysis of 73 plant materials used in bitter tea. <bold>(A)</bold> Families; <bold>(B)</bold> plant parts; <bold>(C)</bold> the number of shared plant materials in areas of Taiwan.</p>
</caption>
<graphic xlink:href="fphar-13-816029-g002.tif"/>
</fig>
<p>The Shannon diversity index for all the 73 medicinal materials in Taiwan was 5.73. Among the northern, central, and southern Taiwan, the medicinal materials used in northern Taiwan were the most diverse, with a Shannon diversity index of 5.27. While the Shannon diversity indices of central and southern Taiwan were 4.92 and 4.11, respectively. Moreover, the more the north, the more species of medicinal materials were used. A total of 49 medicinal materials were used in bitter tea in northern Taiwan, while there were only 34 medicinal materials used in Central Taiwan, and even fewer in southern Taiwan, with only 20 medicinal materials (<xref ref-type="sec" rid="s12">Supplementary Table S3</xref>). In these three areas, only nine medicinal materials were commonly used (<xref ref-type="fig" rid="F2">Figure&#x20;2C</xref>). They were <italic>Tithonia diversifolia</italic> (stem)<italic>, Ixeris chinensis, Rhinacanthus nasutus</italic> (L.) Kurz<italic>, Orthosiphon aristatus</italic> (Blume) Miq.<italic>, Andrographis paniculata</italic> (Burm. f.) Nees<italic>, Solanum incanum, Mallotus repandus</italic> (Willd.) Muell.-Arg.<italic>, Sphagneticola calendulacea</italic> (L.) Pruski<italic>,</italic> and <italic>Pteris multifida</italic>&#x20;Poir.</p>
</sec>
<sec id="s3-3">
<title>Ethnomedicinal Functions of the Bitter Tea</title>
<p>When asked about the traditional applications of the bitter tea sold at a store, all sellers answered based on traditional concepts in Taiwan folk therapy; the bitter flavor is said to protect the liver, and the main ethnomedicinal function of bitter tea is &#x201c;clearing heat, protecting the liver, and lowering liver fire.&#x201d; The sellers also stated that bitter tea is a type of folk therapy product for the&#x20;liver.</p>
<p>The traditional applications of the 73 identified plant materials were revealed, excluding <italic>T. diversifolia</italic> (stem) and&#x20;<italic>A. keiskei</italic> since there were no records on their properties and flavors (<xref ref-type="sec" rid="s12">Supplementary Table S1</xref>). The cold, hot, warm, and cool properties were then analyzed for 71 plant materials; cold properties were the most common (46.5%) followed by cool (26.8%), jointly accounting for 73.3% of the plant material properties (<xref ref-type="fig" rid="F3">Figure&#x20;3A</xref>). Moreover, 69% of the plant materials had a bitter flavor (<xref ref-type="fig" rid="F3">Figure&#x20;3B</xref>). According to a comprehensive analysis of the four properties and five flavors, cold and bitter plants are the most commonly used for preparing bitter tea in Taiwan (<xref ref-type="fig" rid="F3">Figure&#x20;3C</xref>). Analysis of&#x20;the ethnomedicinal function showed that 63.9, 54.8, 25.0, and&#x20;25.0% of the 73 plant materials had heat-clearing, detoxification, detumescence, and diuresis effects, respectively (<xref ref-type="fig" rid="F3">Figure&#x20;3D</xref>).</p>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption>
<p>Traditional and modern pharmacological analysis of plant materials used in Taiwanese bitter tea. <bold>(A)</bold> Nature; <bold>(B)</bold> flavor; <bold>(C)</bold> comprehensive analysis of nature and flavor (%); <bold>(D)</bold> ethnomedicinal effects; <bold>(E)</bold> modern pharmacological applications of plant materials with a frequency greater than&#x20;nine.</p>
</caption>
<graphic xlink:href="fphar-13-816029-g003.tif"/>
</fig>
<p>Among the 24 commonly used plant materials in Taiwanese bitter tea, those with a frequency of use greater than nine were collected to analyze their modern pharmacological applications (<xref ref-type="table" rid="T1">Table&#x20;1</xref>). Anti-inflammation was the most common pharmacological action (<xref ref-type="fig" rid="F3">Figure&#x20;3E</xref>), followed by anticancer, antioxidant, antimicrobial, hepatoprotection, and antidiabetic effects.</p>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Modern pharmacological effects and traditional use of highly cited plant materials used in Taiwanese bitter tea (UV &#x3e; 0.09).</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Voucher specimen numberCMUBT-X<xref ref-type="table-fn" rid="Tfn1">a</xref>
</th>
<th align="center">Scientific name</th>
<th align="center">Family</th>
<th align="center">Local name</th>
<th align="center">Use value (%)</th>
<th align="center">Related research on PubMed</th>
<th align="center">Traditional use</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left">1</td>
<td align="left">
<italic>Andrographis paniculata</italic> (Burm. f.) Nees</td>
<td align="left">
<italic>Acanthaceae</italic>
</td>
<td align="left">Chu&#x101;n x&#x12b;n li&#xe1;n (&#x7a7f;&#x5fc3;&#x84ee;)</td>
<td align="char" char=".">0.31</td>
<td align="left">Antioxidant <xref ref-type="bibr" rid="B131">Mussard et&#x20;al. (2020)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B22">Burgos et&#x20;al. (2020)</xref>, anti-hyperglycemic <xref ref-type="bibr" rid="B201">Wediasari et&#x20;al. (2020)</xref>, hepatoprotective <xref ref-type="bibr" rid="B179">Toppo et&#x20;al. (2021)</xref>, antimicrobial <xref ref-type="bibr" rid="B66">Hossain et&#x20;al. (2021)</xref>, anticancer <xref ref-type="bibr" rid="B118">Malik et&#x20;al. (2021)</xref>, immunomodulatory Liu et&#x20;al. (2020), cardioprotective <xref ref-type="bibr" rid="B103">Lin et&#x20;al. (2020)</xref>, anti-hyperlipidemic, sexual functions and contraceptive <xref ref-type="bibr" rid="B65">Hossain et&#x20;al. (2014)</xref>, antiviral <xref ref-type="bibr" rid="B78">Jadhav and Karuppayil, (2021)</xref>, <xref ref-type="bibr" rid="B154">Sa-Ngiamsuntorn et&#x20;al. (2021)</xref>, anti-snake venom <xref ref-type="bibr" rid="B134">Nayak et&#x20;al. (2021)</xref>, antimalarial <xref ref-type="bibr" rid="B60">Hassan et&#x20;al. (2019)</xref>, anti-Alzheimer <xref ref-type="bibr" rid="B113">Lu et&#x20;al. (2019)</xref>, and anti-obesity <xref ref-type="bibr" rid="B31">Chen et&#x20;al. (2020)</xref>
</td>
<td align="left">Clears heat, resolves toxins, disperses swelling, and relieves pain</td>
</tr>
<tr>
<td align="left">2</td>
<td align="left">
<italic>Tithonia diversifolia (Hemsl.)</italic> A. Gray (stem)</td>
<td align="left">
<italic>Asteraceae (Compositae)</italic>
</td>
<td align="left">W&#x1d4; zh&#x1ce;o j&#x12b;n y&#x12b;ng (&#x4e94;&#x722a;&#x91d1;&#x82f1;)</td>
<td align="char" char=".">0.31</td>
<td align="left">Anti-inflammatory <xref ref-type="bibr" rid="B21">Broering et&#x20;al. (2019)</xref>, antimicrobial, antioxidant <xref ref-type="bibr" rid="B50">Ferreira Farias et&#x20;al. (2019)</xref>, anticancer <xref ref-type="bibr" rid="B115">Lu et&#x20;al. (2017)</xref>, analgesic <xref ref-type="bibr" rid="B141">Owoyele et&#x20;al. (2004)</xref>, anti-hyperlipidemic, antidiabetic <xref ref-type="bibr" rid="B129">Miura et&#x20;al. (2005)</xref>, antiviral <xref ref-type="bibr" rid="B121">Maregesi et&#x20;al. (2010)</xref>, gastroprotective <xref ref-type="bibr" rid="B156">Sanchez-Mendoza et&#x20;al. (2011)</xref>, immunomodulatory <xref ref-type="bibr" rid="B47">Ejelonu et&#x20;al. (2017)</xref>, antimalarial <xref ref-type="bibr" rid="B3">Afolayan et&#x20;al. (2016)</xref>, hepatoprotective <xref ref-type="bibr" rid="B136">Nguepi et&#x20;al. (2021)</xref>, anti-obesity, antiemetic, anti-diarrheal, anti-leishmania, and anti-trypanosoma <xref ref-type="bibr" rid="B117">Mabou Tagne et&#x20;al. (2018)</xref>
</td>
<td align="left">-<xref ref-type="table-fn" rid="Tfn2">b</xref>
</td>
</tr>
<tr>
<td align="left">3</td>
<td align="left">
<italic>Ajuga nipponensis</italic> Makino</td>
<td align="left">
<italic>Lamiaceae</italic>
</td>
<td align="left">B&#xe1;i m&#x1ce; w&#xfa; g&#x14d;ng (&#x767d;&#x99ac;&#x8708;&#x86a3;)</td>
<td align="char" char=".">0.28</td>
<td align="left">Antioxidant, hepatoprotective <xref ref-type="bibr" rid="B68">Hsieh et&#x20;al. (2016)</xref>, and anti-osteoclastogenic <xref ref-type="bibr" rid="B196">Wang, H. et&#x20;al. (2021)</xref>
</td>
<td align="left">Disperses inflammation, cools the blood, and joins bone (Ji&#x113;g&#x1d4;)</td>
</tr>
<tr>
<td align="left">4</td>
<td align="left">
<italic>Ixeris chinensis</italic> (Thunb.) Nakai</td>
<td align="left">
<italic>Asteraceae (Compositae)</italic>
</td>
<td align="left">Xi&#x1ce;o j&#x12b;n y&#x12b;ng (&#x5c0f;&#x91d1;&#x82f1;)</td>
<td align="char" char=".">0.28</td>
<td align="left">Anticancer <xref ref-type="bibr" rid="B212">Xu et&#x20;al. (2016)</xref>, antiviral, hepatoprotective <xref ref-type="bibr" rid="B161">Shih et&#x20;al. (2014)</xref>, immunomodulatory <xref ref-type="bibr" rid="B97">Li et&#x20;al. (2020)</xref>, and antileukemic <xref ref-type="bibr" rid="B35">Chiang et&#x20;al. (2004)</xref>
</td>
<td align="left">Clears heat, promotes urination, and calms the spirit</td>
</tr>
<tr>
<td align="left">5</td>
<td align="left">
<italic>Ilex asprella</italic> (Hook. &#x26; Arn.) Champ. ex Benth</td>
<td align="left">
<italic>Aquifoliaceae</italic>
</td>
<td align="left">W&#xe0;n di&#x1ce;n j&#x12b;n (&#x842c;&#x9ede;&#x91d1;)</td>
<td align="char" char=".">0.25</td>
<td align="left">Anti-inflammatory <xref ref-type="bibr" rid="B215">Yang et&#x20;al. (2018)</xref>, anticancer <xref ref-type="bibr" rid="B98">Li et&#x20;al. (2018)</xref>, immunoregulatory <xref ref-type="bibr" rid="B126">Meng et&#x20;al. (2018)</xref>, lung-protective <xref ref-type="bibr" rid="B43">Dai et&#x20;al. (2014)</xref>, anti-hyperlipidemic <xref ref-type="bibr" rid="B72">Hu et&#x20;al. (2012)</xref>, and antiviral <xref ref-type="bibr" rid="B224">Zhang et&#x20;al. (2018)</xref>
</td>
<td align="left">Clears heat, promotes urination, and calms the spirit</td>
</tr>
<tr>
<td align="left">6</td>
<td align="left">
<italic>Bombax ceiba</italic> L.[<italic>Bombax malabaricum</italic> DC.]</td>
<td align="left">
<italic>Malvaceae[Bombacaceae]</italic>
</td>
<td align="left">M&#xf9; mi&#xe1;n g&#x113;n (&#x6728;&#x68c9;&#x6839;)</td>
<td align="char" char=".">0.22</td>
<td align="left">Antidiabetic <xref ref-type="bibr" rid="B14">Bhargava and Shah (2020)</xref>, antioxidant <xref ref-type="bibr" rid="B89">Komati et&#x20;al. (2020)</xref>, anti-inflammatory, antisteatotic <xref ref-type="bibr" rid="B9">Arafa et&#x20;al. (2019)</xref>, promotes osteoblast proliferation <xref ref-type="bibr" rid="B29">Chauhan et&#x20;al. (2018)</xref>, antimicrobial <xref ref-type="bibr" rid="B160">Shah et&#x20;al. (2018)</xref>, hepatoprotective <xref ref-type="bibr" rid="B94">Lee et&#x20;al. (2017)</xref>, anticancer <xref ref-type="bibr" rid="B188">Tundis et&#x20;al. (2014)</xref>, anti-obesity <xref ref-type="bibr" rid="B58">Gupta et&#x20;al. (2013)</xref>, promotes male sexual function, and antiviral <xref ref-type="bibr" rid="B194">Wang et&#x20;al. (2013)</xref>
</td>
<td align="left">Dispels wind, stops itchiness, dispels wind-dampness, clears heat, resolves toxins, removes stasis, and relives pain</td>
</tr>
<tr>
<td align="left">7</td>
<td align="left">
<italic>Solanum incanum</italic> L</td>
<td align="left">
<italic>Solanaceae</italic>
</td>
<td align="left">Hu&#xe1;ng shu&#x1d0; qi&#xe9;(&#x9ec3;&#x6c34;&#x8304;)</td>
<td align="char" char=".">0.19</td>
<td align="left">Anticancer <xref ref-type="bibr" rid="B209">Wu, Y.H. et&#x20;al. (2015)</xref>, <xref ref-type="bibr" rid="B220">Yu et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B6">Al-Emam et&#x20;al. (2018)</xref> and antimicrobial <xref ref-type="bibr" rid="B93">Lashin et&#x20;al. (2021)</xref>
</td>
<td align="left">Disperses inflammation, resolves toxins, dispels wind, relieves pain, clears heat, and disperses inflammation</td>
</tr>
<tr>
<td align="left">8</td>
<td align="left">
<italic>Mallotus repandus</italic> (Willd.) Muell.-Arg</td>
<td align="left">
<italic>Euphorbiaceae</italic>
</td>
<td align="left">T&#x1d2;ng ji&#x101;o t&#xe9;ng (&#x6876;&#x4ea4;&#x85e4;)</td>
<td align="char" char=".">0.16</td>
<td align="left">Analgesic <xref ref-type="bibr" rid="B59">Hasan et&#x20;al. (2014)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B59">Hasan et&#x20;al. (2014)</xref>, antioxidant <xref ref-type="bibr" rid="B102">Lin et&#x20;al. (1995)</xref>, and hepatoprotective <xref ref-type="bibr" rid="B130">Mondal et&#x20;al. (2020)</xref>
</td>
<td align="left">Clears heat, resolves the exterior, benefits the throat, prevents rashes, improves digestion, disperses swelling, and stops itch</td>
</tr>
<tr>
<td align="left">9</td>
<td align="left">
<italic>Physalis angulata</italic> L</td>
<td align="left">
<italic>Solanaceae</italic>
</td>
<td align="left">D&#x113;ng long c&#x1ce;o (&#x71c8;&#x7c60;&#x8349;)</td>
<td align="char" char=".">0.16</td>
<td align="left">Immunomodulatory <xref ref-type="bibr" rid="B190">Vieceli et&#x20;al. (2021)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B169">Sun, C.P. et&#x20;al. (2017a)</xref>, <xref ref-type="bibr" rid="B170">Sun, C.P. et&#x20;al. (2017b)</xref>, <xref ref-type="bibr" rid="B197">Wang, L. et&#x20;al. (2021)</xref>, antiproliferative <xref ref-type="bibr" rid="B170">Sun, C.P. et&#x20;al. (2017b)</xref>, <xref ref-type="bibr" rid="B23">Chairissy et&#x20;al. (2019)</xref>, antioxidant <xref ref-type="bibr" rid="B1">Adewoye et&#x20;al. (2016)</xref>, reno-restorative <xref ref-type="bibr" rid="B1">Adewoye et&#x20;al. (2016)</xref>, antiparasitic <xref ref-type="bibr" rid="B125">Meira et&#x20;al. (2015)</xref>, antileishmanial <xref ref-type="bibr" rid="B42">Da Silva et&#x20;al. (2018)</xref>, and anticancer <xref ref-type="bibr" rid="B116">Ma et&#x20;al. (2017)</xref>
</td>
<td align="left">Clears heat, resolves toxins, disperses swelling, and removes stasis</td>
</tr>
<tr>
<td align="left">10</td>
<td align="left">
<italic>Rhinacanthus nasutus</italic> (L.) Kurz</td>
<td align="left">
<italic>Acanthaceae</italic>
</td>
<td align="left">B&#xe1;i h&#xe8; l&#xed;ng zh&#x12b;(&#x767d;&#x9db4;&#x9748;&#x829d;)</td>
<td align="char" char=".">0.16</td>
<td align="left">Anticancer <xref ref-type="bibr" rid="B164">Siripong et&#x20;al. (2006)</xref>, <xref ref-type="bibr" rid="B91">Kupradinun et&#x20;al. (2009)</xref>, <xref ref-type="bibr" rid="B162">Siripong et&#x20;al. (2009)</xref>, <xref ref-type="bibr" rid="B63">Horii et&#x20;al. (2012)</xref>, <xref ref-type="bibr" rid="B163">Siripong et&#x20;al. (2012)</xref>, <xref ref-type="bibr" rid="B18">Boueroy et&#x20;al. (2018)</xref>, anti-obesity <xref ref-type="bibr" rid="B135">Ngoc et&#x20;al. (2019)</xref>, anti-glycation <xref ref-type="bibr" rid="B159">Shah et&#x20;al. (2017)</xref>, neuroprotective <xref ref-type="bibr" rid="B39">Chuang et&#x20;al. (2017)</xref>, acetylcholinesterase inhibitor <xref ref-type="bibr" rid="B20">Brimson and Tencomnao, (2011)</xref>, <xref ref-type="bibr" rid="B19">Brimson et&#x20;al. (2012)</xref>, <xref ref-type="bibr" rid="B24">Chang, C.Z. et&#x20;al. (2016)</xref>, <xref ref-type="bibr" rid="B17">Boonyaketgoson et&#x20;al. (2018)</xref>, antioxidant <xref ref-type="bibr" rid="B19">Brimson et&#x20;al. (2012)</xref>, <xref ref-type="bibr" rid="B159">Shah et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B226">Zhao et&#x20;al. (2019)</xref>, antidiabetic <xref ref-type="bibr" rid="B159">Shah et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B191">Visweswara Rao et&#x20;al. (2013a)</xref>, neuraminidase inhibitor <xref ref-type="bibr" rid="B92">Kwak et&#x20;al. (2018)</xref>, hepatoprotective <xref ref-type="bibr" rid="B192">Visweswara Rao et&#x20;al. (2013b)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B226">Zhao et&#x20;al. (2019)</xref>, antimicrobial <xref ref-type="bibr" rid="B85">Kernan et&#x20;al. (1997)</xref>, <xref ref-type="bibr" rid="B148">Puttarak et&#x20;al. (2010)</xref>, <xref ref-type="bibr" rid="B135">Ngoc et&#x20;al. (2019)</xref>, anti-allergic <xref ref-type="bibr" rid="B174">Tewtrakul et&#x20;al. (2009)</xref>, immunomodulatory <xref ref-type="bibr" rid="B147">Punturee et&#x20;al. (2005)</xref>, anti-Parkinson&#x2019;s <xref ref-type="bibr" rid="B155">Saleem et&#x20;al. (2021)</xref>, and antifungal <xref ref-type="bibr" rid="B79">Jeenkeawpieam et&#x20;al. (2020)</xref>
</td>
<td align="left">Moistens the lung and stops coughing, calms the liver and reduces fire, disperses swelling, resolves toxins, kills worms, and stops itchiness</td>
</tr>
<tr>
<td align="left">11</td>
<td align="left">
<italic>Sigesbeckia orientalis</italic> L</td>
<td align="left">
<italic>Asteraceae (Compositae)</italic>
</td>
<td align="left">K&#x1d4; c&#x1ce;o (&#x82e6;&#x8349;)X&#x12b; li&#xe0;n c&#x1ce;o (&#x8c68;&#x859f;&#x8349;)</td>
<td align="char" char=".">0.16</td>
<td align="left">Antimicrobial, anti-allergic, antithrombotic <xref ref-type="bibr" rid="B198">Wang, Q. et&#x20;al. (2021)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B137">Nguyen et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B38">Chu et&#x20;al. (2018)</xref>, <xref ref-type="bibr" rid="B48">Engels et&#x20;al. (2020)</xref>, antihyperuricemic <xref ref-type="bibr" rid="B137">Nguyen et&#x20;al. (2017)</xref>, analgesic <xref ref-type="bibr" rid="B137">Nguyen et&#x20;al. (2017)</xref>, and anticancer <xref ref-type="bibr" rid="B171">Sun and Wang, (2006)</xref>, <xref ref-type="bibr" rid="B25">Chang, C.C. et&#x20;al. (2016)</xref>
</td>
<td align="left">Dispels wind-dampness and benefits sinew and bone</td>
</tr>
<tr>
<td align="left">12</td>
<td align="left">
<italic>Boehmeria nivea</italic> (L.) Gaudich.[<italic>Boehmeria nivea</italic> (L.) Gaudich. var. <italic>tenacissima</italic> (Gaudich.) Miq.]</td>
<td align="left">
<italic>Urticaceae</italic>
</td>
<td align="left">Sh&#x101;n zh&#xf9; m&#xe1;(&#x5c71;&#x82e7;&#x9ebb;)</td>
<td align="char" char=".">0.13</td>
<td align="left">Anti-inflammatory <xref ref-type="bibr" rid="B99">Lim et&#x20;al. (2020)</xref>, laxative, antioxidant <xref ref-type="bibr" rid="B95">Lee et&#x20;al. (2020)</xref>, and antiproliferative <xref ref-type="bibr" rid="B195">Wang et&#x20;al. (2019)</xref>
</td>
<td align="left"/>
</tr>
<tr>
<td align="left">13</td>
<td align="left">
<italic>Glycyrrhiza uralensis</italic> Fisch</td>
<td align="left">
<italic>Leguminosae</italic>
</td>
<td align="left">G&#x101;n c&#x1ce;o (&#x7518;&#x8349;)</td>
<td align="char" char=".">0.13</td>
<td align="left">Anticancer, antiulcer, spasmolytic, hepatoprotective, anti-inflammatory, antimicrobial <xref ref-type="bibr" rid="B80">Jiang et&#x20;al. (2020)</xref>, and anti-allergic <xref ref-type="bibr" rid="B51">Fouladi et&#x20;al. (2019)</xref>
</td>
<td align="left">Supplements the spleen, boosts qi, relaxes tension, relieves pain, moistens lungs, stops coughing, drains fire, resolves toxins, and harmonizes the activity of other medicines</td>
</tr>
<tr>
<td align="left">14</td>
<td align="left">
<italic>Orthosiphon aristatus</italic> (Blume) Miq</td>
<td align="left">
<italic>Lamiaceae</italic>
</td>
<td align="left">Hu&#xe0; sh&#xed; c&#x1ce;o (&#x5316;&#x77f3;&#x8349;)</td>
<td align="char" char=".">0.13</td>
<td align="left">Genoprotective <xref ref-type="bibr" rid="B5">Al-Dualimi et&#x20;al. (2018)</xref>, antibacterial <xref ref-type="bibr" rid="B5">Al-Dualimi et&#x20;al. (2018)</xref>, antidiabetic <xref ref-type="bibr" rid="B44">Damsud et&#x20;al. (2014)</xref>, antioxidant <xref ref-type="bibr" rid="B70">Hsu et&#x20;al. (2010)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B70">Hsu et&#x20;al. (2010)</xref>, and antihypertensive <xref ref-type="bibr" rid="B122">Matsubara et&#x20;al. (1999)</xref>, <xref ref-type="bibr" rid="B139">Ohashi et&#x20;al. (2000)</xref>
</td>
<td align="left">Clears heat, promotes urination, and clears kidney stones</td>
</tr>
<tr>
<td align="left">15</td>
<td align="left">
<italic>Platostoma palustre</italic> (Blume) A.J.Paton [<italic>Mesona chinensis</italic> Benth.]</td>
<td align="left">
<italic>Lamiaceae</italic>
</td>
<td align="left">Xi&#x101;n c&#x1ce;o (&#x4ed9;&#x8349;)</td>
<td align="char" char=".">0.13</td>
<td align="left">Antidiabetic <xref ref-type="bibr" rid="B2">Adisakwattana et&#x20;al. (2014)</xref>, <xref ref-type="bibr" rid="B41">Chusak et&#x20;al. (2014)</xref>, <xref ref-type="bibr" rid="B109">Liu S. et&#x20;al. (2018)</xref>, <xref ref-type="bibr" rid="B221">Yuris et&#x20;al. (2019)</xref> and antioxidant <xref ref-type="bibr" rid="B73">Huang et&#x20;al. (2019)</xref>, <xref ref-type="bibr" rid="B74">Huang, L. et&#x20;al. (2020)</xref>
</td>
<td align="left">Clears heat and resolves toxins</td>
</tr>
<tr>
<td align="left">16</td>
<td align="left">
<italic>Bidens pilosa</italic> L.[<italic>Bidens pilosa</italic> L. var. <italic>radiata</italic> Sch. Bip.]</td>
<td align="left">
<italic>Asteraceae (Compositae)</italic>
</td>
<td align="left">Xi&#xe1;n f&#x113;ng c&#x1ce;o (&#x54b8;&#x8c50;&#x8349;)</td>
<td align="char" char=".">0.09</td>
<td align="left">Anticancer <xref ref-type="bibr" rid="B10">Arantes et&#x20;al. (2021)</xref>, gastroprotective <xref ref-type="bibr" rid="B7">Alvarez et&#x20;al. (1999)</xref>, <xref ref-type="bibr" rid="B64">Horiuchi et&#x20;al. (2010)</xref>, Anti-diabetic <xref ref-type="bibr" rid="B37">Chien et&#x20;al. (2009)</xref>, <xref ref-type="bibr" rid="B189">Ubillas et&#x20;al. (2000)</xref> Anti-allergy <xref ref-type="bibr" rid="B123">Matsumoto et&#x20;al. (2009)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B62">Hong et&#x20;al. (2021)</xref>, <xref ref-type="bibr" rid="B211">Xin et&#x20;al. (2021)</xref> Anti-malaria <xref ref-type="bibr" rid="B132">Nadia et&#x20;al. (2020)</xref> Anti-microbial <xref ref-type="bibr" rid="B36">Chiavari-Frederico et&#x20;al. (2020)</xref> anti-coccidial, <xref ref-type="bibr" rid="B214">Yang et&#x20;al. (2019)</xref>, hepatoprotective <xref ref-type="bibr" rid="B144">Pegoraro et&#x20;al. (2021)</xref>, and anti-hypertensive <xref ref-type="bibr" rid="B15">Bilanda et&#x20;al. (2017)</xref>
</td>
<td align="left">Clears heat, resolves toxins, promotes urination, and reduces jaundice</td>
</tr>
<tr>
<td align="left">17</td>
<td align="left">
<italic>Elephantopus scaber</italic> L</td>
<td align="left">
<italic>Asteraceae (Compositae)</italic>
</td>
<td align="left">Ding sh&#xf9; w&#x16b;(&#x4e01;&#x8c4e;&#x6747;)</td>
<td align="char" char=".">0.09</td>
<td align="left">Anticancer <xref ref-type="bibr" rid="B12">Bai et&#x20;al. (2020)</xref>, <xref ref-type="bibr" rid="B143">Pandey et&#x20;al. (2020)</xref>, hepatoprotective <xref ref-type="bibr" rid="B168">Sulistyani and Nurkhasanah, (2020)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B52">Fu et&#x20;al. (2020)</xref>, <xref ref-type="bibr" rid="B149">Qi et&#x20;al. (2020)</xref>, antioxidant <xref ref-type="bibr" rid="B11">Aslam et&#x20;al. (2016)</xref>, antidiabetic, antimicrobial, and analgesic <xref ref-type="bibr" rid="B61">Hiradeve and Rangari, (2014)</xref>
</td>
<td align="left">Clears heat, resolves toxins, promotes urination, and disperses swelling</td>
</tr>
<tr>
<td align="left">18</td>
<td align="left">
<italic>Momordica charantia</italic> L.[<italic>Momordica charantia</italic> L. var. <italic>abbreviata</italic> Ser.]</td>
<td align="left">
<italic>Cucurbitaceae</italic>
</td>
<td align="left">Sh&#x101;n k&#x1d4; gu&#x101;(&#x5c71;&#x82e6;&#x74dc;)</td>
<td align="char" char=".">0.09</td>
<td align="left">Anti-obesity <xref ref-type="bibr" rid="B49">Fan et&#x20;al. (2021)</xref>, anti-fatigue <xref ref-type="bibr" rid="B67">Hsiao et&#x20;al. (2017)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B145">Perera et&#x20;al. (2021)</xref>, <xref ref-type="bibr" rid="B186">Tsai et&#x20;al. (2016)</xref>, antioxidant <xref ref-type="bibr" rid="B4">Akyuz et&#x20;al. (2020)</xref>, cell-protective <xref ref-type="bibr" rid="B185">Tsai et&#x20;al. (2014)</xref>, antimelanogenic <xref ref-type="bibr" rid="B185">Tsai et&#x20;al. (2014)</xref>, antidiabetic <xref ref-type="bibr" rid="B90">Kulkarni et&#x20;al. (2021)</xref>, and anticancer <xref ref-type="bibr" rid="B46">Ehigie et&#x20;al. (2021)</xref>
</td>
<td align="left">Dispels wind, clears heat, clears the liver, and brightens the eyes</td>
</tr>
<tr>
<td align="left">19</td>
<td align="left">
<italic>Mucuna macrocarpa</italic> Wall</td>
<td align="left">
<italic>Leguminosae</italic>
</td>
<td align="left">Xi&#x11b; t&#xe9;ng (&#x8840;&#x85e4;)</td>
<td align="char" char=".">0.09</td>
<td align="left">Antileukemic <xref ref-type="bibr" rid="B114">Lu et&#x20;al. (2010)</xref>
</td>
<td align="left">Cures rheumatic pain (backache)</td>
</tr>
<tr>
<td align="left">20</td>
<td align="left">
<italic>Oldenlandia diffusa</italic> (Willd.) Roxb.[<italic>Hedyotis diffusa</italic> Willd.]</td>
<td align="left">
<italic>Rubiaceae</italic>
</td>
<td align="left">B&#xe1;i hu&#x101; sh&#xe9; sh&#xe9; c&#x1ce;o (&#x767d;&#x82b1;&#x86c7;&#x820c;&#x8349;)</td>
<td align="char" char=".">0.09</td>
<td align="left">Anticancer <xref ref-type="bibr" rid="B40">Chung et&#x20;al. (2017)</xref>, immunomodulatory, antioxidant <xref ref-type="bibr" rid="B34">Chen et&#x20;al. (2016)</xref>, and anti-inflammatory <xref ref-type="bibr" rid="B229">Zhu et&#x20;al. (2018)</xref>
</td>
<td align="left">Clears heat, resolves toxins, engenders fluid, relieves thirst, and invigorates the blood</td>
</tr>
<tr>
<td align="left">21</td>
<td align="left">
<italic>Pteris multifida</italic> Poir</td>
<td align="left">
<italic>Pteridaceae</italic>
</td>
<td align="left">F&#xe8;ng w&#x11b;i c&#x1ce;o (&#x9cf3;&#x5c3e;&#x8349;)</td>
<td align="char" char=".">0.09</td>
<td align="left">Anti-cancer <xref ref-type="bibr" rid="B86">Kim et&#x20;al. (2017)</xref>, anti-neuroinflammatory <xref ref-type="bibr" rid="B87">Kim et&#x20;al. (2016)</xref>, anti-hyperlipidemic <xref ref-type="bibr" rid="B199">Wang et&#x20;al. (2010)</xref>, free radical-scavenging activity <xref ref-type="bibr" rid="B200">Wang et&#x20;al. (2007)</xref>, and anti-inflammatory <xref ref-type="bibr" rid="B217">Yin et&#x20;al. (2018)</xref>
</td>
<td align="left">Clears heat, promotes urination, cools the blood, and resolves toxins</td>
</tr>
<tr>
<td align="left">22</td>
<td align="left">
<italic>Scutellaria barbata</italic> D. Don</td>
<td align="left">
<italic>Lamiaceae</italic>
</td>
<td align="left">B&#xe0;n zh&#x12b; li&#xe1;n (&#x534a;&#x679d;&#x84ee;)</td>
<td align="char" char=".">0.09</td>
<td align="left">Anti-inflammatory<xref ref-type="bibr" rid="B4">Akyuz et&#x20;al. (2020)</xref>, <xref ref-type="bibr" rid="B106">Liu H.L. et&#x20;al. (2018)</xref>, anticancer<xref ref-type="bibr" rid="B30">Chen et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B54">Gao et&#x20;al. (2014)</xref>, <xref ref-type="bibr" rid="B82">Jin et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B84">Kan et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B101">Lin et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B120">Marconett et&#x20;al. (2010)</xref>, <xref ref-type="bibr" rid="B142">Ozmen et&#x20;al. (2010)</xref>, <xref ref-type="bibr" rid="B172">Sun, P. et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B222">Zhang et&#x20;al. (2017)</xref>, <xref ref-type="bibr" rid="B223">Zhang et&#x20;al. (2021)</xref>, antiproliferative <xref ref-type="bibr" rid="B88">Kim et&#x20;al. (2008)</xref>, <xref ref-type="bibr" rid="B207">Wu and Chen, (2009)</xref>, attenuates diabetic retinopathy <xref ref-type="bibr" rid="B124">Mei et&#x20;al. (2017)</xref>, neuroprotective <xref ref-type="bibr" rid="B206">Wu et&#x20;al. (2016)</xref>, improves cognition <xref ref-type="bibr" rid="B225">Zhang and Li, (2016)</xref>, antimicrobial <xref ref-type="bibr" rid="B158">Sato et&#x20;al. (2000)</xref>, <xref ref-type="bibr" rid="B205">Wu, T. et&#x20;al. (2015)</xref>, <xref ref-type="bibr" rid="B218">Yu et&#x20;al. (2004)</xref>, acaricidal <xref ref-type="bibr" rid="B213">Yang et&#x20;al. (2013)</xref>, and antioxidant <xref ref-type="bibr" rid="B216">Ye and Huang, (2012)</xref>
</td>
<td align="left">Clears heat, resolves toxins, invigorates the blood, eliminates stasis, disperses swelling, relieves pain, and cures cancer</td>
</tr>
<tr>
<td align="left">23</td>
<td align="left">
<italic>Sphagneticola calendulacea</italic> (L.) Pruski [<italic>Wedelia chinensis</italic> (Osbeck) Merr.]</td>
<td align="left">
<italic>Asteraceae (Compositae)</italic>
</td>
<td align="left">Hu&#xe1;ng hu&#x101; m&#xec; c&#xe0;i (&#x9ec3;&#x82b1;&#x871c;&#x83dc;)</td>
<td align="char" char=".">0.09</td>
<td align="left">Antidiabetic <xref ref-type="bibr" rid="B33">Chen et&#x20;al. (2021)</xref>, <xref ref-type="bibr" rid="B175">Thao et&#x20;al. (2018)</xref>, anticancer <xref ref-type="bibr" rid="B76">Huang et&#x20;al. (2016)</xref>, <xref ref-type="bibr" rid="B100">Lin et&#x20;al. (2007)</xref>, <xref ref-type="bibr" rid="B108">Liu, M. et&#x20;al. (2013)</xref>, <xref ref-type="bibr" rid="B180">Tsai et&#x20;al. (2009)</xref>, <xref ref-type="bibr" rid="B181">Tsai et&#x20;al. (2015)</xref>, <xref ref-type="bibr" rid="B182">Tsai et&#x20;al. (2017a)</xref>, <xref ref-type="bibr" rid="B183">Tsai et&#x20;al. (2017b)</xref>, neuroprotective <xref ref-type="bibr" rid="B105">Lin et&#x20;al. (2014)</xref>, antibacterial <xref ref-type="bibr" rid="B45">Darah et&#x20;al. (2013)</xref>, anti-inflammatory <xref ref-type="bibr" rid="B45">Darah et&#x20;al. (2013)</xref>, and antioxidant <xref ref-type="bibr" rid="B119">Manjamalai and Berlin Grace, (2012)</xref>
</td>
<td align="left">Clears heat, resolves toxins, eliminates stasis, and disperses swelling</td>
</tr>
<tr>
<td align="left">24</td>
<td align="left">
<italic>Tithonia diversifolia</italic> (Hemsl.) A.Gray (leaf)</td>
<td align="left">
<italic>Asteraceae (Compositae)</italic>
</td>
<td align="left">W&#x1d4; zh&#x1ce;o j&#x12b;n y&#x12b;ng y&#xe8;(&#x4e94;&#x722a;&#x91d1;&#x82f1;&#x8449;)</td>
<td align="char" char=".">0.09</td>
<td align="left">Hepatoprotective <xref ref-type="bibr" rid="B136">Nguepi et&#x20;al. (2021)</xref>, cardioprotective <xref ref-type="bibr" rid="B77">Ide et&#x20;al. (2020)</xref>, antioxidant, antimicrobial <xref ref-type="bibr" rid="B50">Ferreira Farias et&#x20;al. (2019)</xref>, antidiabetic, immunomodulatory, analgesic, antimalarial, anti-obesity, anti-hyperlipidemic, gastroprotective, antiemetic, antidiarrheal, antileishmanial, anti-trypanosomal, antivenin, and antiviral <xref ref-type="bibr" rid="B117">Mabou Tagne et&#x20;al. (2018)</xref>
</td>
<td align="left">Clears heat, resolves toxins, disperses swelling, and relieves pain</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="Tfn1">
<label>a</label>
<p>CMUBT, china medical university bitter&#x20;tea.</p>
</fn>
<fn id="Tfn2">
<label>b</label>
<p>No records for the stem of <italic>T. diversifolia</italic> in the Committee on Chinese Medicine and Pharmacy (2003) and the second edition of The Committee on Chinese Medicine and Pharmacy (2011).</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3-4">
<title>Comparison Between Taiwanese Bitter Tea and Green Herb Tea</title>
<p>We next compared the top 15 most commonly used plant materials between Taiwanese bitter tea and green herb tea&#x20;(<xref ref-type="fig" rid="F4">Figure&#x20;4A</xref>) and found an overlap of only four&#x20;plant&#x20;materials: <italic>Glycyrrhiza uralensis</italic> Fisch., <italic>P. palustre</italic>, <italic>I. asprella</italic>, and <italic>Rhinacanthus nasutus</italic> (L.) Kurz. Therefore, the plant materials used vary between these two tea&#x20;types.</p>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption>
<p>Comparisons between Taiwanese bitter tea and green herb tea. <bold>(A)</bold> Venn diagram of the top 15 most commonly used plant materials in bitter tea and green herb tea. <bold>(B)</bold> Comparison of the nature and flavor of the plant materials. <bold>(C)</bold> Use values of the top five most commonly used plant materials (1&#x2013;5 indicate the top five commonly used plant materials). The horizontal dotted line indicates the highest UV of BT. <bold>(D)</bold> Modern pharmacological applications of the top 15 most commonly used plant materials. QCC, qing-cao-cha (green herb tea); BT, bitter&#x20;tea.</p>
</caption>
<graphic xlink:href="fphar-13-816029-g004.tif"/>
</fig>
<p>Plant materials with a bitter flavor were then divided into bitter cold and sweet cold; bitter cold plant materials accounted for 37.1 and 21.4% of the bitter tea and green herb tea plant materials, respectively, whereas sweet cold plants were used in the same proportion of approximately 19% (<xref ref-type="fig" rid="F4">Figure&#x20;4B</xref>). The UV values of the top five most commonly used plant materials were higher for green herb tea than for bitter tea (<xref ref-type="fig" rid="F4">Figure&#x20;4C</xref>). Moreover, the composition of green herb tea sold in different stores was shown to have minimal differences and high consistency, whereas the constituents of bitter tea differed among businesses in Taiwan. Therefore, the selection of plant materials for bitter tea is not consistent.</p>
<p>Anti-inflammation is the most published aspect in plant&#x20;pharmacology research associated with the top 15 most commonly used plant materials in bitter tea and green herb tea (<xref ref-type="fig" rid="F4">Figure&#x20;4D</xref>). For green herb tea, this is followed by antioxidant, antimicrobial, and anticancer effects, which is slightly different than that for bitter tea (<xref ref-type="fig" rid="F4">Figure&#x20;4D</xref>).</p>
</sec>
<sec id="s3-5">
<title>Comparison of Taiwanese Bitter Tea With That of Herbal Tea From Lingnan, Chaoshan, and Fujian</title>
<p>In the south of China near Taiwan, there are other local herbal&#x20;teas (liang-cha; cool tea) that are commonly consumed.&#x20;Comparisons of Taiwanese bitter tea with herbal teas&#x20;from the Lingnan area (<xref ref-type="bibr" rid="B111">Liu Y. et&#x20;al., 2013</xref>), Chaoshan area (<xref ref-type="bibr" rid="B96">Li et&#x20;al., 2017</xref>), and Fujian (<xref ref-type="bibr" rid="B104">Lin, 2014</xref>) revealed that the plant materials used in herbal teas vary across the four locations. Notably, 35 (48.0%) of the plant materials used in bitter tea, according to the survey, were limited to Taiwan (<xref ref-type="fig" rid="F5">Figure&#x20;5</xref>).</p>
<fig id="F5" position="float">
<label>FIGURE 5</label>
<caption>
<p>Venn diagram showing the number of shared plant materials in herbal tea from different regions.</p>
</caption>
<graphic xlink:href="fphar-13-816029-g005.tif"/>
</fig>
</sec>
<sec id="s3-6">
<title>Analysis of High-Frequency Drug Pairs and Core Network Analysis of Taiwanese Bitter Tea</title>
<p>To identify the drug pairs used in high frequencies, we performed core network analysis. Eight drug pairs appeared more than four times in 32 formulations and included nine medicinal plant materials from <italic>A. paniculata</italic>, <italic>I. asprella</italic>, <italic>T. diversifolia</italic>, <italic>A. nipponensis</italic>, <italic>Mallotus repandus</italic> (Willd.) Muell.-Arg., <italic>Bombax ceiba</italic> L., <italic>Solanum incanum</italic> L., and <italic>I. chinensis</italic>. The most commonly used drug pairs were <italic>A. paniculata</italic>&#x2013;<italic>A. nipponensis</italic> and <italic>A. paniculata</italic>&#x2013;<italic>I. asprella</italic>, with a frequency of occurrence of 5 in 32 formulations.</p>
<p>We constructed a network diagram (<xref ref-type="fig" rid="F6">Figure&#x20;6</xref>) of the core components of Taiwanese bitter tea using TCMISS v2.5, and found that the core medicinal materials were from <italic>A. nipponensis</italic> and <italic>T. diversifolia.</italic> The medicinal plants often matched with <italic>A. nipponensis</italic> were <italic>I. chinensis</italic>, <italic>A. paniculata</italic>, and <italic>T. diversifolia</italic>, whereas those often matched with <italic>T. diversifolia</italic> were <italic>A. nipponensis</italic>, <italic>I. asprella</italic>, and <italic>M. repandus</italic> surrounded by <italic>T. diversifolia</italic>, <italic>M. repandus</italic>, and <italic>S. incanum</italic>.</p>
<fig id="F6" position="float">
<label>FIGURE 6</label>
<caption>
<p>Network analysis of the high frequency drug pairs found in Taiwanese bitter tea. The number is the UV of the plant material, and the length of the connecting line indicates co-occurrence frequency. The circle sizes represent the relative ratio of UV. AN, <italic>Ajuga nipponensis</italic> Makino; IC, <italic>Ixeris chinensis</italic> (Thunb.) Nakai; IA, <italic>Ilex asprella</italic> (Hook. &#x26; Arn.) Champ.; TD, <italic>Tithonia diversifolia</italic> (Hemsl.) A. Gray; MR, <italic>Mallotus repandus</italic> (Willd.) M&#xfc;ll. Arg.; BM, <italic>Bombax malabarica</italic> DC.; SI, <italic>Solanum incanum</italic> L.; AP, <italic>Andrographis paniculat</italic>a (Burm. f.) Nees.</p>
</caption>
<graphic xlink:href="fphar-13-816029-g006.tif"/>
</fig>
</sec>
</sec>
<sec sec-type="discussion" id="s4">
<title>Discussion</title>
<p>In ethnopharmacological research, the method of field surveys have been used to explore the medicinal plants and traditional medicines prescribed for certain diseases in different regions. Topics related to medicinal botanicals that employed field investigation in the past include quality control of authentic medicinal materials (<xref ref-type="bibr" rid="B227">Zhao et&#x20;al., 2012</xref>), green herb tea (Huang et&#x20;al., 2020), herbal tea (Liu et&#x20;al., 2013; <xref ref-type="bibr" rid="B96">Li et&#x20;al., 2017</xref>), medicinal diets (<xref ref-type="bibr" rid="B173">Tan et&#x20;al., 2017</xref>), and herbal compositions of lactation promoting herbs (<xref ref-type="bibr" rid="B28">Chao et&#x20;al., 2020</xref>). In the present study, the field survey was adopted on Taiwanese bitter tea. We surveyed and analyzed the formulations of Taiwanese bitter tea, a special herbal tea commonly consumed in Taiwan, and revealed its current status in terms of ingredients and function.</p>
<p>Most of the identified plant materials in the study belonged to the family Asteraceae and Lamiaceae. The high involvement of Asteraceae and Lamiaceae in Taiwanese bitter tea is consistent with some other investigations in folk medicine outside Taiwan. They are two of the &#x201c;hot families&#x201d; in the medical plants (<xref ref-type="bibr" rid="B157">Saslis-Lagoudakis et&#x20;al., 2011</xref>). Medicinal plants of the two families are dominant in Mediterranean (<xref ref-type="bibr" rid="B56">Gras et&#x20;al., 2018</xref>), Ugandan (<xref ref-type="bibr" rid="B187">Tugume and Nyakoojo, 2019</xref>), Turkish (<xref ref-type="bibr" rid="B57">G&#xfc;ne&#x15f; et&#x20;al., 2017</xref>), Lebanese (Baydoun et&#x20;al., 2015), Peruvian (<xref ref-type="bibr" rid="B151">Rehecho et&#x20;al., 2011</xref>), Jordanian (<xref ref-type="bibr" rid="B8">Alzweiri et&#x20;al., 2011</xref>), and Algerian (<xref ref-type="bibr" rid="B150">Rachid et&#x20;al., 2012</xref>) folk medicines. Asteraceae exhibits high environmental adaptability and hosts a large number of naturalized and invasive plants globally. In addition, the climate in Taiwan is conducive for Asteraceae growth, and plants in this family are the third most abundant vascular plants in Taiwan, making them very easy to obtain in the wild (<xref ref-type="bibr" rid="B152">Rolnik and Olas, 2021</xref>). Asteraceae plants also possess numerous and diverse flavors. The Lamiaceae family is the second largest source of plant raw materials used in Taiwanese bitter tea. Lamiaceae family plants are characterized by high amounts of volatile oils, and thus the plants are extensively used as culinary herbs (<xref ref-type="bibr" rid="B133">Napoli et&#x20;al., 2020</xref>). Previous studies have reported that the volatile oils of these plants have antioxidant, anti-inflammatory, and antibacterial properties (<xref ref-type="bibr" rid="B138">Nieto, 2017</xref>), which may explain why Lamiaceae is widely used in herbal tea. This study also found several naturalized plants that were introduced from America and Africa used in bitter tea. American native plants introduced into Taiwan and used in bitter tea included <italic>Physalis angulata</italic> L., <italic>Bidens pilosa</italic> L., and <italic>Tithonia diversifolia</italic>, and African native plants included <italic>Solanum incanum</italic> L. and <italic>Momordica charantia</italic> L. (<xref ref-type="bibr" rid="B204">Wu et&#x20;al., 2004</xref>).</p>
<p>The diversity analysis for the northern, central, and southern Taiwan revealed that the more the north, the more diversity of medicinal materials were. Northern Taiwan is the political and economic center of Taiwan, with very little land to grow and correct plants. The medicinal materials used in northern Taiwan are usually imported from other areas. On the other hand, the central and southern areas of Taiwan grow more plants, including medicinal plants, and have more wild land, where wild medicinal plants could be collected. Therefore, medicinal materials used by stores in the central and southern Taiwan were more readily available and more restricted locally than those in northern Taiwan. This is the reason we speculated for the more number of medicinal materials and higher diversity in Northern Taiwan than in other&#x20;areas.</p>
<p>All participants in the survey reported that the main function of bitter tea is to protect the liver. A previous study on green herb tea in Taiwan also reported similar results (<xref ref-type="bibr" rid="B32">Chen and Lin, 2012</xref>). We suspected that this result is associated with the past high prevalence of hepatitis B in Taiwan, with 15&#x2013;20% of the population being chronic hepatitis B carriers. Although the Taiwanese government promoted large-scale vaccination initiatives for newborns that reduced the incidence of hepatitis B (<xref ref-type="bibr" rid="B193">Wait and Chen, 2012</xref>), hepatitis C&#x2014;a major cause of liver cirrhosis and liver cancer&#x2014;is still prevalent in Taiwan (<xref ref-type="bibr" rid="B219">Yu et&#x20;al., 2020</xref>). According to the cause of death statistics, chronic liver disease and liver cirrhosis remain among the top 10 causes of death, with liver cancer part of the top 10 cancers in Taiwan (<xref ref-type="bibr" rid="B127">Ministry of Health and Welfare, 2019</xref>). Therefore, people seek local plant materials that can &#x201c;protect the liver&#x201d; and provide &#x201c;liver protection.&#x201d; Therefore, Taiwanese bitter tea may have developed as a medicinal drink under such circumstances.</p>
<p>Taiwanese bitter tea was mainly composed of cold and cool plant materials. According to theory of traditional Chinese medicine, cold and cool plants have a &#x201c;heat clearing&#x201d; effect, which can treat &#x201c;heat syndrome&#x201d;. Heat syndrome refers to symptoms such as redness, fever, inflammation, yellow and red urine, and dry stool (<xref ref-type="bibr" rid="B167">Su et&#x20;al., 2013</xref>). In the survey, many storekeepers mentioned that the components rendering the bitter flavor can enter the liver and that plant raw materials of bitter plants have liver &#x201c;fire reduction&#x201d; effects. Therefore, Taiwanese bitter tea is used to reduce &#x201c;liver fire&#x201d; and improve liver health. Other commonly used traditional Chinese medicines with bitter flavor for treating liver diseases include <italic>Gentiana scabra</italic> Bunge, <italic>Artemisia capillaris</italic>, and <italic>S. baicalensis</italic> (<xref ref-type="bibr" rid="B184">Tsai et&#x20;al., 2020</xref>). In addition, bitterness-imparting compounds have been extracted from <italic>Artemisia</italic> absinthium L., a medicinal plant with hepatoprotective effects and a strong bitter taste that has been traditionally used in Europe.</p>
<p>During our analysis of the use and properties of Taiwanese bitter tea plant materials in the literature, we found that hepatoprotection was the fifth most published aspect for the 24 most commonly used plant materials and the fourth for the top 15 plant materials by frequency. Plants with high UV values, such as <italic>A. paniculate</italic> (<xref ref-type="bibr" rid="B65">Hossain et&#x20;al., 2014</xref>), <italic>A. nipponensis</italic> (<xref ref-type="bibr" rid="B68">Hsieh et&#x20;al., 2016</xref>), and <italic>T. diversifolia</italic> (<xref ref-type="bibr" rid="B117">Mabou Tagne et&#x20;al., 2018</xref>) were reported to have hepatoprotective effects in pharmacological studies, whereas <italic>I. chinensis</italic> was reported to have antiviral effects against the hepatitis B virus. Meanwhile, hepatoprotection was ranked sixth for Taiwanese green herb tea. The most frequently reported pharmacological action of plant materials in bitter tea was anti-inflammation, followed by anticancer, antioxidant, antimicrobial, and anti-glycosuria effects. Long-term chronic inflammation can cause excessive oxidative stress, which is a major cause of cancer development (<xref ref-type="bibr" rid="B16">Bishayee, 2014</xref>); therefore, anti-inflammatories and antioxidants are considered to have potential roles in preventing cancer. For Taiwanese green herb tea, the most reported pharmacological action for the plant materials was anti-inflammation, followed by antioxidant, antimicrobial, and anticancer (Huang et&#x20;al., 2020). According to these data, Taiwanese green herb tea has similar benefits to those of bitter tea; however, bitter tea may have stronger hepatoprotective effects than does green herb&#x20;tea.</p>
<p>A comparison of the composition of Taiwanese bitter tea with three popular herbal drinks from Lingnan (<xref ref-type="bibr" rid="B111">Liu Y. et&#x20;al., 2013</xref>), Chaoshan (<xref ref-type="bibr" rid="B96">Li et&#x20;al., 2017</xref>), and Fujian (<xref ref-type="bibr" rid="B104">Lin, 2014</xref>) revealed that 11 (15.1%) plants were used in common. Moreover, there are 35 (48%) plants used only in Taiwanese bitter tea but not used in the cool teas of the above-mentioned three areas of southern mainland China. Nevertheless, the functions of herbal teas advertised in these three regions in southern China are similar to those of herbal teas in Taiwan, all of which are used to &#x201c;clear internal heat&#x201d;. Similarly, several medicinal plants used in herbal teas in the Lingnan, Chaoshan, and Fujian were been reported to have antioxidant, anti-inflammatory (<xref ref-type="bibr" rid="B208">Wu et&#x20;al., 2020</xref>), and hepatoprotective (<xref ref-type="bibr" rid="B13">Bao et&#x20;al., 2008</xref>) properties in pharmacological studies. However, given that almost half of the plant materials used in Taiwanese bitter tea are not used in herbal teas from Lingnan, Chaoshan, and Fujian, Taiwanese bitter tea can be regarded as a unique herbal&#x20;tea.</p>
<p>The store owners selling Taiwanese bitter tea had a wide age distribution. Seventy-six percent of the source of knowledge on plant materials used in Taiwanese bitter tea was information passed down over generations. Generally, the herbal tea industry is traditional and conservative, and the recipes are often restricted within families and are not shared with external parties. Such conservative practices in the tea industry are gradually being abandoned. According to a study on herbal tea culture in Taiwan, the sale of herbal tea in Taiwan has decreased, with the number of traditional stores gradually declining (<xref ref-type="bibr" rid="B32">Chen and Lin, 2012</xref>). The findings of the present study can facilitate the preservation of these ancient family recipes as well as the cultural heritage of Taiwanese bitter tea through the Taiwanese government, the field of ethnopharmacology, and the food and pharmaceutical industries.</p>
</sec>
<sec sec-type="conclusion" id="s5">
<title>Conclusion</title>
<p>Bitter tea is a major traditional drink in Taiwan. The findings of the present study indicate that Taiwanese bitter tea is a very diverse mixture without a clear core species used in all these mixture. Moreover, the plant materials used in Taiwanese bitter tea are unique and that the constituent plants have numerous functions. More follow-up studies are required to ascertain the pharmacological effects of Taiwanese bitter tea; facilitate safer and more effective use of bitter tea in Taiwan; and preserve bitter tea as a traditional culture and resource.</p>
</sec>
</body>
<back>
<sec id="s6">
<title>Data Availability Statement</title>
<p>The original contributions presented in the study are included in the article/<xref ref-type="sec" rid="s12">Supplementary Material</xref>, further inquiries can be directed to the corresponding authors.</p>
</sec>
<sec id="s7">
<title>Ethics Statement</title>
<p>The studies involving human participants were reviewed and approved by the CRREC-107&#x2013;019. The patients/participants provided their written informed consent to participate in this study.</p>
</sec>
<sec id="s8">
<title>Author Contributions</title>
<p>S-SH, T-YC, J-SD, L-HP, Y-CC, S-YS, and JC designed the study. S-SH, T-YC, J-SD, S-YS, and JC conducted the field work. S-SH, T-YC, L-HP, and JC performed the data analysis. S-SH, T-YC, Y-CC, and JC wrote the manuscript. All authors contributed to the article and approved the submitted version.</p>
</sec>
<sec id="s9">
<title>Funding</title>
<p>This work was supported by the Ministry of Science and Technology (grant numbers MOST 107-2320-B-039-030-MY3, MOST 107-2320-B-039-063, MOST 108-2813-C-039-061-B and MOST 109-2320-B-039-026); China Medical University (Grant Number CMU106-N-24, CMU107-N-33, CMU109-MF-95, CMU108-MF-116, CMU-108-SR-101, and CMU108-N-22); Chang Gung Memorial Hospital (Chang Gung Medical Research Program grant number CMRPF1D0123); and the Higher Education Sprout Project and Teaching Practice Research Program of China Medical University (Grant Number 1077170A) and Ministry of Education, Taiwan.</p>
</sec>
<sec sec-type="COI-statement" id="s10">
<title>Conflict of Interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="disclaimer" id="s11">
<title>Publisher&#x2019;s Note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<ack>
<p>The authors are grateful to the herbarium of China Medical University for providing us with a space for storing the&#x20;medicinal materials collected during this study. The&#x20;authors would like to thank Editage for editorial assistance.</p>
</ack>
<sec id="s12">
<title>Supplementary Material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fphar.2022.816029/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fphar.2022.816029/full&#x23;supplementary-material</ext-link>
</p>
<supplementary-material xlink:href="DataSheet1.docx" id="SM1" mimetype="application/docx" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
<fn-group>
<fn id="fn2">
<label>1</label>
<p>
<ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/pubmed">https://www.ncbi.nlm.nih.gov/pubmed</ext-link>
</p>
</fn>
<fn id="fn3">
<label>2</label>
<p>
<ext-link ext-link-type="uri" xlink:href="http://bioinformatics.psb.ugent.be/webtools/Venn/">http://bioinformatics.psb.ugent.be/webtools/Venn/</ext-link>
</p>
</fn>
</fn-group>
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