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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>Rhus chinensis</italic> and <italic>Galla Chinensis</italic> – folklore to modern evidence: review</title><author><name sortKey="Djakpo, Odilon" sort="Djakpo, Odilon" uniqKey="Djakpo O" first="Odilon" last="Djakpo">Odilon Djakpo</name><affiliation><nlm:aff id="af1"></nlm:aff></affiliation><affiliation><nlm:aff id="af2"></nlm:aff></affiliation></author><author><name sortKey="Yao, Weirong" sort="Yao, Weirong" uniqKey="Yao W" first="Weirong" last="Yao">Weirong Yao</name><affiliation><nlm:aff id="af1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20564459</idno><idno type="pmc">7167973</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167973</idno><idno type="RBID">PMC:7167973</idno><idno type="doi">10.1002/ptr.3215</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000979</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000979</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>Rhus chinensis</italic> and <italic>Galla Chinensis</italic> – folklore to modern evidence: review</title><author><name sortKey="Djakpo, Odilon" sort="Djakpo, Odilon" uniqKey="Djakpo O" first="Odilon" last="Djakpo">Odilon Djakpo</name><affiliation><nlm:aff id="af1"></nlm:aff></affiliation><affiliation><nlm:aff id="af2"></nlm:aff></affiliation></author><author><name sortKey="Yao, Weirong" sort="Yao, Weirong" uniqKey="Yao W" first="Weirong" last="Yao">Weirong Yao</name><affiliation><nlm:aff id="af1"></nlm:aff></affiliation></author></analytic><series><title level="j">Phytotherapy Research</title><idno type="ISSN">0951-418X</idno><idno type="eISSN">1099-1573</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p>The species <italic>Rhus chinensis</italic> Mill. (Anacardiaceae) is an important representative of the genus <italic>Rhus</italic>, which contains over 250 individual species found in temperate and tropical regions worldwide. <italic>Rhus chinensis</italic> has long been used by folk medicine practitioners in Asia. Leaves, roots, stem, bark, fruit and particularly the galls on <italic>Rhus chinensis</italic> leaves, <italic>Galla chinensis</italic>, are recognized to have preventative and therapeutic effects on different ailments (such as diarrhea, dysentery, rectal and intestinal cancer, diabetes mellitus, sepsis, oral diseases and inflammation). However, it is critical to separate evidence from anecdote. Fortunately, recent scientific research has revealed that <italic>Rhus chinensis</italic> compounds possess strong antiviral, antibacterial, anticancer, hepatoprotective, antidiarrheal and antioxidant activities. Moreover, compounds isolated from the stem of <italic>Rhus chinensis </italic>significantly suppressed HIV‐1 activity <italic>in vitro</italic>. Compounds from this plant were also found to inhibit enamel demineralization <italic>in vitro</italic> and enhance remineralization of dental enamel with fluoride. This review highlights claims from traditional and tribal medicinal lore and makes a contemporary summary of phytochemical, biological and pharmacological findings on this plant material. It aims to show that the pharmaceutical potential of this plant deserves closer attention. Copyright © 2010 John Wiley & Sons, Ltd.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Phytother Res</journal-id><journal-id journal-id-type="iso-abbrev">Phytother Res</journal-id><journal-id journal-id-type="doi">10.1002/(ISSN)1099-1573</journal-id><journal-id journal-id-type="publisher-id">PTR</journal-id><journal-title-group><journal-title>Phytotherapy Research</journal-title></journal-title-group><issn pub-type="ppub">0951-418X</issn><issn pub-type="epub">1099-1573</issn><publisher><publisher-name>John Wiley & Sons, Ltd.</publisher-name><publisher-loc>Chichester, UK</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20564459</article-id><article-id pub-id-type="pmc">7167973</article-id><article-id pub-id-type="doi">10.1002/ptr.3215</article-id><article-id pub-id-type="publisher-id">PTR3215</article-id><article-categories><subj-group subj-group-type="overline"><subject>Review Article</subject></subj-group><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title><italic>Rhus chinensis</italic> and <italic>Galla Chinensis</italic> – folklore to modern evidence: review</article-title><alt-title alt-title-type="right-running-head"><italic>RHUS CHINENSIS</italic> AND <italic>GALLA CHINENSIS</italic></alt-title></title-group><contrib-group><contrib id="au1" contrib-type="author" corresp="yes"><name><surname>Djakpo</surname><given-names>Odilon</given-names></name><xref ref-type="aff" rid="af1"><sup>1</sup></xref><xref ref-type="aff" rid="af2"><sup>2</sup></xref><address><email>odj563@gmail.com</email></address></contrib><contrib id="au2" contrib-type="author"><name><surname>Yao</surname><given-names>Weirong</given-names></name><xref ref-type="aff" rid="af1"><sup>1</sup></xref></contrib></contrib-group><aff id="af1"><label><sup>1</sup></label>School of Food Science and Technology, Jiangnan University, Food Safety and Quality Control Laboratory, Wuxi, 214122, Jiangsu Province, P.R. China</aff><aff id="af2"><label><sup>2</sup></label>Université d'Abomey‐calavi, Faculté des Sciences Agronomiques, Département de Nutrition et Sciences Alimentaires, Abomey‐calavi, 01 BP 526 Benin</aff><author-notes><corresp id="correspondenceTo"><label>*</label>Food Safety and Quality Control Laboratory, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, P.R. China</corresp></author-notes><pub-date pub-type="epub"><day>22</day><month>11</month><year>2010</year></pub-date><pub-date pub-type="ppub"><month>12</month><year>2010</year></pub-date><volume>24</volume><issue>12</issue><issue-id pub-id-type="doi">10.1002/ptr.v24:12</issue-id><fpage>1739</fpage><lpage>1747</lpage><history><date date-type="received"><day>15</day><month>1</month><year>2010</year></date><date date-type="rev-recd"><day>29</day><month>3</month><year>2010</year></date><date date-type="accepted"><day>11</day><month>4</month><year>2010</year></date></history><permissions><copyright-statement content-type="article-copyright">Copyright © 2010 John Wiley & Sons, Ltd.</copyright-statement><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="file:PTR-24-1739.pdf"></self-uri><abstract><title>Abstract</title><p>The species <italic>Rhus chinensis</italic> Mill. (Anacardiaceae) is an important representative of the genus <italic>Rhus</italic>, which contains over 250 individual species found in temperate and tropical regions worldwide. <italic>Rhus chinensis</italic> has long been used by folk medicine practitioners in Asia. Leaves, roots, stem, bark, fruit and particularly the galls on <italic>Rhus chinensis</italic> leaves, <italic>Galla chinensis</italic>, are recognized to have preventative and therapeutic effects on different ailments (such as diarrhea, dysentery, rectal and intestinal cancer, diabetes mellitus, sepsis, oral diseases and inflammation). However, it is critical to separate evidence from anecdote. Fortunately, recent scientific research has revealed that <italic>Rhus chinensis</italic> compounds possess strong antiviral, antibacterial, anticancer, hepatoprotective, antidiarrheal and antioxidant activities. Moreover, compounds isolated from the stem of <italic>Rhus chinensis </italic>significantly suppressed HIV‐1 activity <italic>in vitro</italic>. Compounds from this plant were also found to inhibit enamel demineralization <italic>in vitro</italic> and enhance remineralization of dental enamel with fluoride. This review highlights claims from traditional and tribal medicinal lore and makes a contemporary summary of phytochemical, biological and pharmacological findings on this plant material. It aims to show that the pharmaceutical potential of this plant deserves closer attention. Copyright © 2010 John Wiley & Sons, Ltd.</p></abstract><kwd-group kwd-group-type="author-generated"><kwd id="kwd1"><italic>Rhus chinensis</italic></kwd><kwd id="kwd2"><italic>Galla chinensis</italic></kwd><kwd id="kwd3">traditional medicine</kwd><kwd id="kwd4">pharmacology</kwd><kwd id="kwd5">antiviral</kwd><kwd id="kwd6">anticaries</kwd><kwd id="kwd7">triterpene</kwd><kwd id="kwd8">gallotannins</kwd></kwd-group><counts><fig-count count="1"></fig-count><table-count count="1"></table-count><ref-count count="109"></ref-count><page-count count="9"></page-count></counts><custom-meta-group><custom-meta><meta-name>source-schema-version-number</meta-name><meta-value>2.0</meta-value></custom-meta><custom-meta><meta-name>cover-date</meta-name><meta-value>December 2010</meta-value></custom-meta><custom-meta><meta-name>details-of-publishers-convertor</meta-name><meta-value>Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="sec1-1"><title>INTRODUCTION</title><p><italic>Rhus chinensis</italic> belongs to the genus <italic>Rhus</italic> and the Family <italic>Anacardiaceae </italic>(Miller <italic>et al.</italic>, <xref rid="bib63" ref-type="ref">2001</xref>). Commonly called sumac, <italic>Rhus</italic> consists of approximately 250 individual species of flowering plants, with six species found (four endemics) in China. Like most sumacs, <italic>Rhus chinensis</italic> is a dioecious shrub that can reach 8 m in height. It bears odd pinnately compound leaves and creamy‐white flowers. The fruits (drupes) are orange or red in color at maturity and contain one seed (Barkley, <xref rid="bib8" ref-type="ref">1937</xref>; Miller <italic>et al.</italic>, <xref rid="bib63" ref-type="ref">2001</xref>; Tianlu and Barfod, <xref rid="bib92" ref-type="ref">2008</xref>). The species grows in areas with marginal agricultural capacity, and is widely distributed in temperate, subtropical, and tropical regions, including China, Japan, Malaysia, Taiwan and India (Rayne and Mazza, <xref rid="bib81" ref-type="ref">2007</xref>; Ren <italic>et al.</italic>, <xref rid="bib82" ref-type="ref">2008</xref>).</p><p>The species <italic>Rhus chinensis</italic> has two distinct varieties, <italic>Rhus chinensis </italic>var. chinensis<italic> (syn. Rhus semialata</italic>; <italic>Rhus semialata</italic> var. osbeckii; <italic>Rhus osbeckii) </italic>and <italic>Rhus chinensis </italic>var. roxburghii <italic>(Syn. Rhus semialata</italic> var. roxburghii; <italic>Rhus javanica</italic> Linnaeus var. roxburghii; <italic>Rhus roxburghii)</italic> (Tianlu and Barfod, <xref rid="bib92" ref-type="ref">2008</xref>; GRIN; TROPICOS).</p><p><italic>Galla chinensis</italic> or <italic>Galla rhois</italic> is the term used to describe the gall caused by the Chinese aphid, <italic>Schlechtendalia chinensis</italic> (Bell), on the leaves of <italic>Rhus chinensis</italic> (Lee <italic>et al.</italic>, <xref rid="bib53" ref-type="ref">1997</xref>). This gall is widely used as a separate drug. Other species in this genus also produce galls that are considered to have an inferior quality.</p><p>A plethora of traditional medicine references claim curative power for <italic>Rhus chinensis</italic>, despite its widespread use, many of these claims of efficacy were not supported by scientific evidence, whether for traditional use validation or for drug development endeavors.</p><p>Fortunately, recent scientific research on <italic>Rhus chinensis</italic> has revealed promising health benefits, including anticancer, antiviral, antimicrobial, antidiarrheal and antiinflammatory properties (Yang et al., <xref rid="bib101" ref-type="ref">2005</xref>; Gu <italic>et al.</italic>, <xref rid="bib30" ref-type="ref">2007</xref>; Ahn <italic>et al.</italic>, <xref rid="bib3" ref-type="ref">1998</xref>; Chen <italic>et al.</italic>, <xref rid="bib15" ref-type="ref">2009</xref>; Kim et al., <xref rid="bib45" ref-type="ref">2005</xref>). In recent years, the Chinese herbal medicine <italic>Galla chinensis</italic> has been discussed widely as a new alternative for carious disease (Chu <italic>et al.</italic>, <xref rid="bib21" ref-type="ref">2007</xref>).</p><p>So far, no comprehensive review has been compiled from the literature encompassing the efficacy of this plant. Widespread claims of the medicinal effectiveness of various <italic>Rhus chinensis</italic> tree preparations motivated us to bridge the information gap in this area.</p></sec><sec id="sec1-2"><title>TRADITIONAL MEDICINAL USE</title><p>Among <italic>Rhus </italic>species, <italic>Rhus chinensis </italic>and its gall, <italic>Galla chinensis,</italic> have a long history of use by indigenous peoples for medicinal care and others. Numerous curative properties are ascribed to different parts of this tree, namely root, bark, stem, leaf, fruit, flowers, seed and gall (Table <xref rid="tbl1" ref-type="table">1</xref>). The leaves and the root are used as depuratives, stimulating blood circulation. Its decoction is used in the treatment of hemoptysis, inflammations, laryngitis, snakebite, stomachache and traumatic fractures (Duke and Ayensu, <xref rid="bib24" ref-type="ref">1985</xref>; Kao, <xref rid="bib40" ref-type="ref">1988</xref>; Ouyang <italic>et al.</italic>, <xref rid="bib71" ref-type="ref">2008</xref>). The ripe fruits of this plant have long been used in Asia to treat dysentery and diarrhea, as well as other gastrointestinal disorders (Kala, <xref rid="bib37" ref-type="ref">2005</xref>; Pradhan and Badola, <xref rid="bib80" ref-type="ref">2008</xref>; Bose et al., <xref rid="bib10" ref-type="ref">2008</xref>). The fruit produces a sour juice when boiled with water. This juice, when diluted with water or/and mixed with raw eggs, treats diarrhea and dysentery (Pradhan and Badola, <xref rid="bib80" ref-type="ref">2008</xref>). It is used for the treatment of colic (Chopra <italic>et al.</italic>, <xref rid="bib20" ref-type="ref">1986</xref>) and also as a food preservative (Pradhan and Badola, <xref rid="bib80" ref-type="ref">2008</xref>). The seed is used in the treatment of cough, dysentery, fever, jaundice, malaria and rheumatism (Duke and Ayensu, <xref rid="bib24" ref-type="ref">1985</xref>; Abbasi <italic>et al.</italic>, <xref rid="bib1" ref-type="ref">2009</xref>).</p><table-wrap id="tbl1" xml:lang="en" orientation="portrait" position="float"><label>Table 1</label><caption><p>Summary of traditional medicinal uses of <italic>Rhus chinensis</italic></p></caption><table frame="hsides" rules="groups"><col span="1"></col><col span="1"></col><col span="1"></col><thead valign="bottom"><tr style="border-bottom:solid 1px #000000"><th align="left" valign="bottom" rowspan="1" colspan="1">Plant parts</th><th align="left" valign="bottom" rowspan="1" colspan="1">Medicinal use</th><th align="left" valign="bottom" rowspan="1" colspan="1">References</th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" rowspan="1" colspan="1">Leaves</td><td align="left" valign="top" rowspan="1" colspan="1">Depurative, can stimulate blood circulation, hemoptysis, inflammations, laryngitis, stomachache , traumatic fractures, spermatorrhea, snake bite, antitussive, diarrhea</td><td align="left" valign="top" rowspan="1" colspan="1">Duke and Ayensu, 1985; Kao, 1988; Ouyang <italic>et al.</italic>, 2008; Xiao, 1989</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Fruits</td><td align="left" valign="top" rowspan="1" colspan="1">Colic, diarrhea, dysentery, jaundice and hepatitis</td><td align="left" valign="top" rowspan="1" colspan="1">Chopra <italic>et al.</italic>, 1986;Tangpu and Yadav, 2004; Kala, 2005; Pradhan and Badola, 2008; Abbasi <italic>et al.</italic>, 2009</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Seeds</td><td align="left" valign="top" rowspan="1" colspan="1">Coughs, dysentery, fever, jaundice, hepatitis, malaria and rheumatism</td><td align="left" valign="top" rowspan="1" colspan="1">Duke and Ayensu, 1985; Abbasi <italic>et al.</italic>, 2009</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Root</td><td align="left" valign="top" rowspan="1" colspan="1">Diarrhea, spermatorrhea, malaria, antitussives, treatments of anasarca, jaundice and snake bite</td><td align="left" valign="top" rowspan="1" colspan="1">Kao, 1988; Xiao, 1989; Ouyang <italic>et al.</italic>, 2008; Duke and Ayensu, 1985; Abbasi <italic>et al.</italic>, 2009</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Galls</td><td align="left" valign="top" rowspan="1" colspan="1">Diarrhea, diabetes mellitus, antiseptic, antiphlogistic, astringent, haemostatic, persistent cough with blood, spontaneous sweating, urorrhoea, bloody sputum, burns, hemorrhoids, oral diseases, fever, malaria, inflammation, toxicosis, sore, skin infections, rectal and intestinal cancer</td><td align="left" valign="top" rowspan="1" colspan="1">Duke and Ayensu, 1985; Zhu, 1998; Hupkens <italic>et al.</italic>, 1995; Tian <italic>et al.,</italic> 2009a; Ho <italic>et al.,</italic> 2002; Yeung, 1985; Gao <italic>et al.,</italic> 2000; Tian <italic>et al.</italic>, 2009; Kee and Walter, 1999</td></tr></tbody></table><permissions><copyright-holder>John Wiley & Sons, Ltd.</copyright-holder><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions></table-wrap><p>The gall of <italic>Rhus chinensis</italic> has long been considered to possess natural medicinal properties with numerous benefits (Zhang <italic>et al.</italic>, <xref rid="bib105" ref-type="ref">2009</xref>). <italic>Galla chinensis</italic> is used internally for its astringent properties to treat disease such as diarrhea and hemorrhage (Duke and Ayensu, <xref rid="bib24" ref-type="ref">1985</xref>). It is a frequent ingredient in polyherbal prescriptions for diabetes mellitus (Duke and Ayensu, <xref rid="bib24" ref-type="ref">1985</xref>). It has hemostatic effects, often used to promote clotting following traumatic injuries and to treat burns (Yeung, <xref rid="bib102" ref-type="ref">1985</xref>). It is also used to treat rectal and intestinal cancer, prolapse of the rectum, seminal enuresis and hemorrhoids (Yeung, <xref rid="bib102" ref-type="ref">1985</xref>; Gao <italic>et al.</italic>, <xref rid="bib27" ref-type="ref">2000</xref>). In addition to its antiphlogistic and antiseptic uses for treating diseases such as persistent cough, <italic>Galla chinensis</italic> also has antiinflammatory properties (Tian <italic>et al.</italic>, 2009). It is also used to counteract ulcers in the mouth and to treat fever and malaria (Duke and Ayensu, <xref rid="bib24" ref-type="ref">1985</xref>; Gao <italic>et al.</italic>, <xref rid="bib27" ref-type="ref">2000</xref>).</p></sec><sec id="sec1-3"><title>PHYTOCHEMISTRY</title><p>Phytochemical studies on <italic>Rhus</italic> species have been reported earlier and resulted in the characterization of several compound groups such as flavonoids (Taniguchi <italic>et al.</italic>, <xref rid="bib88" ref-type="ref">2000</xref>; Lee <italic>et al.</italic>, <xref rid="bib57" ref-type="ref">2005</xref>; Lin <italic>et al.</italic>, <xref rid="bib59" ref-type="ref">2008</xref>), triterpenoids (Kuo, 1991; Parveen, 1991; Lee <italic>et al.</italic>, <xref rid="bib57" ref-type="ref">2005</xref>), phenolics (Parveen and Khan, <xref rid="bib75" ref-type="ref">1988</xref>; Lee <italic>et al.</italic>, <xref rid="bib57" ref-type="ref">2005</xref>; Ouyang <italic>et al.</italic>, <xref rid="bib71" ref-type="ref">2008</xref>), tannins (Takechi <italic>et al.</italic>, <xref rid="bib86" ref-type="ref">1985</xref>) and aromatic alkanes (Kuo et al., <xref rid="bib46" ref-type="ref">1991</xref>; Lee <italic>et al.</italic>, <xref rid="bib57" ref-type="ref">2005</xref>; Ouyang <italic>et al.</italic>, <xref rid="bib71" ref-type="ref">2008</xref>).</p><p>The galls on <italic>Rhus chinensis</italic> leaves are rich in gallotannin (50–70%), a type of hydrolysable tannin (Kee and Walter, <xref rid="bib43" ref-type="ref">1999</xref>; Xiao <italic>et al.</italic>, <xref rid="bib100" ref-type="ref">2000</xref>). Gallotannins from <italic>Galla chinensis</italic> consist of a central glucose core, which is surrounded by several gallic acid units, and further gallic acid units can be attached through depside bonding of additional galloyl residues. Structures containing 1 to 14 galloyl residues result from such processes, yielding tri‐, tetra‐, penta‐, hepta‐ and nonagalloylglucose, and others (Xiang <italic>et al.</italic>, <xref rid="bib98" ref-type="ref">2007</xref>; Tian <italic>et al.</italic>, <xref rid="bib90" ref-type="ref">2009b</xref>). Pentagalloylglucose [<bold>1</bold>], 3‐galloyl‐gallic acid and 4‐galloyl‐gallic acid isomers isolated from <italic>Galla chinensis</italic> are reported to be the primary bioactive gallotannins, possessing numerous medicinal activities and health benefits (An <italic>et al.</italic>, <xref rid="bib5" ref-type="ref">2005</xref>; Sakai <italic>et al.</italic>, <xref rid="bib83" ref-type="ref">1990</xref>; Bhimani <italic>et al.</italic>, <xref rid="bib9" ref-type="ref">1993</xref>; Feldman <italic>et al.</italic>, <xref rid="bib25" ref-type="ref">2001</xref>; Choi <italic>et al.</italic>, <xref rid="bib17" ref-type="ref">2002</xref>). <italic>Rhus chinensis </italic>is rich in well known phenolic compounds, gallic acid [<bold>2</bold>] and methyl gallate [<bold>3</bold>] (Ahn <italic>et al.</italic>, <xref rid="bib3" ref-type="ref">1998</xref>, <xref rid="bib4" ref-type="ref">2005</xref>; Bae <italic>et al.</italic>, <xref rid="bib7" ref-type="ref">1998</xref>; Choi <italic>et al.</italic>, <xref rid="bib19" ref-type="ref">2009</xref>). According to Buziashvili <italic>et al.</italic> (<xref rid="bib11" ref-type="ref">1973</xref>) <italic>Galla chinensis</italic> is composed of nearly 20% gallic acid and 7% methyl gallate.</p><p>A new benzofuranone, 5‐hydroxy‐3‐(propan‐2‐ylidene)‐7‐(3,7,11,15‐tetramethylhexade‐ca‐ 2,6,10,11‐tetraenyl)‐2(3H)‐benzofuranone [<bold>4</bold>], together with 16 known bioactive compounds, including 5‐hydroxy‐7‐(3,7,11,15‐tetramethylhexadeca‐ 2,6,10,11‐tetraenyl)‐ 2(3H)‐benzofuranone [<bold>5</bold>], 3‐oxo‐6β‐hydroxyolean‐12‐en‐28‐oic acid [<bold>6</bold>], 3‐oxo‐6β‐hydroxyolean‐18‐en‐28‐oic acid [<bold>7</bold>] moronic acid [<bold>8</bold>], betulonic acid [<bold>9</bold>], gallicin [<bold>10</bold>], dihydroxytoluene [<bold>11</bold>] and dimethylcaffic acid [<bold>12</bold>], have been isolated from the root stem of <italic>Rhus chinensis </italic>(Gu <italic>et al.</italic>, <xref rid="bib30" ref-type="ref">2007</xref>; Wang et al., <xref rid="bib95" ref-type="ref">2008</xref>).</p><p>Phenol glycosides and lariciresinol‐based ligan glycosides compounds have been shown to be present in the butanol extract of <italic>Rhus chinensis</italic> root (Ouyang <italic>et al.</italic>, <xref rid="bib70" ref-type="ref">2007</xref>, <xref rid="bib71" ref-type="ref">2008</xref>). 6‐Pentadecylsalicylic acid, an antithrombotic compound [13] (Kuo, 1991) and fisetin (3,7,3‐,4‐tetrahydroxyflavone) [<bold>14</bold>] (Lee <italic>et al.</italic>, <xref rid="bib57" ref-type="ref">2005</xref>) an antiinflammatory, have also been isolated from the stem of <italic>Rhus chinensis</italic>. The leaves of this plant are rich in essential oils, with palmitic acid, phytol and <italic>n</italic>‐heptacosane as the major components (Zhu <italic>et al.</italic>, <xref rid="bib106" ref-type="ref">2007</xref>).</p></sec><sec id="sec1-4"><title>BIOLOGICAL AND PHARMACOLOGICAL PROPERTIES</title><sec id="sec2-1"><title>Antibacterial activity</title><p>The high level of gallotannins along with phenolic compounds, gallic acid and methyl gallate, known antimicrobial agents make <italic>Galla chinensis</italic> very useful in bacterial control (Wu‐Yuan <italic>et al.</italic>, <xref rid="bib97" ref-type="ref">1988</xref>; Ahn <italic>et al.</italic>, <xref rid="bib3" ref-type="ref">1998</xref>; Kang <italic>et al.</italic>, <xref rid="bib39" ref-type="ref">2008</xref>; Tian <italic>et al.</italic>, <xref rid="bib89" ref-type="ref">2009a</xref>, <xref rid="bib90" ref-type="ref">2009b</xref>). Extracts from <italic>Galla chinensis</italic> inhibited several bacteria such as <italic>Bacillus subtilis</italic>, <italic>B. cereus</italic>, <italic>Escherichia coli</italic>, <italic>Enterobacter cloacae</italic>, <italic>Helicobacter pylori</italic>, <italic>Klebsiella oxytoca</italic>, <italic>Lactobacillus casei</italic>, <italic>L. acidophilus</italic>, <italic>L. salivarius</italic>, <italic>Salmonella derby</italic>, <italic>S. minesota</italic>, <italic>S. typhimurium</italic>, <italic>S. enteritidis</italic>, <italic>Shigella dysenteriae</italic>, <italic>Staphylococcus aureus</italic>, <italic>Streptococcus mutans</italic>, <italic>S. sobrinus</italic>, <italic>Ureaplasma urealyticum</italic>, with the minimal inhibitory concentration (MIC) in the range 0.5–8 mg/mL (Wu‐Yuan <italic>et al.</italic>, <xref rid="bib97" ref-type="ref">1988</xref>, Bae <italic>et al.</italic>, <xref rid="bib7" ref-type="ref">1998</xref>; Choi II <italic>et al.</italic>, <xref rid="bib17" ref-type="ref">2002</xref>; Kang <italic>et al.</italic>, <xref rid="bib39" ref-type="ref">2008</xref>; Zhu <italic>et al.</italic>, <xref rid="bib107" ref-type="ref">2008</xref>; Choi <italic>et al.</italic>, <xref rid="bib19" ref-type="ref">2009</xref>; Tian <italic>et al.</italic>, <xref rid="bib89" ref-type="ref">2009a</xref>).</p><p>Tian <italic>et al.</italic> (<xref rid="bib90" ref-type="ref">2009b</xref>) reported that different gallotannins from <italic>Galla chinensis</italic> separated according to the number of galloylglucose had significant antibacterial activities on <italic>Bacillus cereus</italic> and <italic>Salmonella typhimurium.</italic> Structure activity relationship studies indicated that antibacterial activity was positively correlated with the numbers of galloyl groups and generally, gallotannins with higher molecular weights had strong antibacterial activities (Tian et al., <xref rid="bib89" ref-type="ref">2009a</xref>, <xref rid="bib90" ref-type="ref">2009b</xref>).</p><p>A methanol extract of <italic>Galla chinensis</italic> was shown to have significant growth‐inhibitory activity towards harmful intestinal bacteria (Ahn et al., <xref rid="bib2" ref-type="ref">1994</xref>, <xref rid="bib3" ref-type="ref">1998</xref>). Activity‐directed fractionation of the methanol extract of <italic>Galla chinensis</italic> has led to the isolation of gallic acid and its derivative methyl gallate as the major components involved in the observed antimicrobial activity.</p><p>It was also reported that methyl gallate and gallic acid from <italic>Galla chinensis </italic>had inhibitory effects on periodontopathic bacteria (MIC = 1 mg/mL) and significantly reduced the <italic>in vitro</italic> biofilm formation of <italic>S. mutans</italic> (methyl gallate, 1 mg/mL gallic acid, 4 mg/mL, <italic>p</italic> < 0.05) (Kang <italic>et al.</italic>, <xref rid="bib39" ref-type="ref">2008</xref>).</p></sec><sec id="sec2-2"><title>Antiviral activities</title><sec id="sec3-1"><title>Anti‐HIV activity.</title><p>In a recent study, different fractions of <italic>Rhus chinensis</italic> showed potent anti‐HIV‐1 activity (Wang <italic>et al.</italic>, <xref rid="bib94" ref-type="ref">2006</xref>). Subsequent anti‐HIV guided fractionation <italic>of Rhus chinensis </italic>led to the isolation of 17 compounds with potent anti‐HIV‐1 activity (Gu <italic>et al.</italic>, <xref rid="bib30" ref-type="ref">2007</xref>; Wang <italic>et al.</italic>, <xref rid="bib95" ref-type="ref">2008</xref>). Among those compounds, a new class of benzofuranone‐type compounds 5‐hydroxy‐3‐(propan‐2‐ylidene)‐7‐(3,7,11,15‐tetramethylhexadeca‐2,6,10,11‐tetraenyl)‐2(3H)‐benzofuranone [<bold>4</bold>] and 5‐hydroxy‐7‐(3,7,11,15‐tetramethylhexadeca‐ 2,6,10,11‐tetraenyl)‐2(3H)‐benzofuranone [<bold>5</bold>] were found significantly to suppress HIV‐1 replication (Gu <italic>et al.</italic>, <xref rid="bib30" ref-type="ref">2007</xref>). Compound [<bold>4</bold>] possessed significant anti‐HIV‐1 activity with a therapeutic index (TI) of 42.40, whereas compound [<bold>5</bold>] showed moderate anti‐HIV‐1 activity with a TI of 3.28 (Gu <italic>et al.</italic>, <xref rid="bib30" ref-type="ref">2007</xref>). Furthermore, the action mechanisms of the two benzofuranone‐type compounds were investigated by Wang <italic>et al.</italic> (<xref rid="bib95" ref-type="ref">2008</xref>). These authors found that both compounds [<bold>4</bold>] and [<bold>5</bold>] inhibited HIV‐1 replication in chronically infected H9 cells and may target late‐stages of the HIV‐1 life cycle.</p><p>Betulonic acid [<bold>9</bold>] an analogue of betulinic acid, a well known anti‐HIV‐1 agent (Kashiwada <italic>et al.</italic>, <xref rid="bib41" ref-type="ref">1996</xref>; Soler <italic>et al.</italic>, <xref rid="bib85" ref-type="ref">1996</xref>) exhibited moderate anti‐HIV‐1 activity with a TI value of 5.27–8.94 µm (Gu <italic>et al.</italic>, <xref rid="bib30" ref-type="ref">2007</xref>; Wang <italic>et al.</italic>, <xref rid="bib95" ref-type="ref">2008</xref>).</p><p>3‐Oxo‐6β‐hydroxyolean‐12‐en‐28‐oic acid [<bold>6</bold>], 3‐oxo‐6β‐hydroxyolean‐18‐en‐28‐oic acid [<bold>7</bold>] and moronic acid [<bold>8</bold>] are oleanolic acid‐related triterpenes previously reported to have potential anti‐HIV‐1 activity (Pengsuparp <italic>et al.</italic>, <xref rid="bib77" ref-type="ref">1994</xref>; Soler <italic>et al.</italic>, <xref rid="bib85" ref-type="ref">1996</xref>; Kashiwada <italic>et al.</italic>, <xref rid="bib42" ref-type="ref">1998</xref>). These compounds showed weak anti‐HIV activity with TI values of 4.14, 4.74 and 8.22, respectively (Gu <italic>et al.</italic>, <xref rid="bib30" ref-type="ref">2007</xref>; Wang <italic>et al.</italic>, <xref rid="bib95" ref-type="ref">2008</xref>). Mengoni <italic>et al.</italic> (<xref rid="bib62" ref-type="ref">2002</xref>) described the anti‐HIV and the mechanism of action for oleanolic acid, both of which suggested that oleanolic acid inhibits HIV‐1 protease activity <italic>in vitro</italic>.</p><p>Gallicins [<bold>10</bold>], gallic acid derivate‐type compounds, have been reported to inhibit HIV‐1 integrase (Kim <italic>et al.</italic>, <xref rid="bib44" ref-type="ref">1998</xref>). The work of Wang <italic>et al.</italic> (<xref rid="bib95" ref-type="ref">2008</xref>) confirmed the result in cell lines with a therapeutic index of 5.11. Dihydroxytoluene [<bold>11</bold>] had the same extent of anti‐HIV‐1 activity with a TI of 5.34. Wang and coworkers also showed that dimethylcaffic acid [<bold>12</bold>], caffeic acid phenylethyl ester derivate, has potent anti‐HIV‐1 activity with a TI value of 19.07.</p><p>These values are relatively low compared with the control AZT (TI > 471883) but the resistance and the adverse side effects to available conventional anti‐HIV drugs beg the need of identification and development of additional small‐molecule inhibitors that can be used in combination with currently available antiviral agents.</p></sec><sec id="sec3-2"><title>Anti herpes simplex virus activity.</title><p><italic>In vivo </italic>studies performed in mice have shown that the hot‐water extract of <italic>Rhus chinensis</italic> had prophylactic and therapeutic efficacy against herpes simplex virus (HSV) type 1 (HSV‐1) (Kurokawa <italic>et al.</italic>, <xref rid="bib51" ref-type="ref">1993</xref>, <xref rid="bib49" ref-type="ref">1995a</xref>, <xref rid="bib52" ref-type="ref">1995b</xref>, 1997). This extract was also effective against acyclovir‐resistant HSV‐1 and HSV type 2 (HSV‐2) infections in mice (Kurokawa <italic>et al.</italic>, <xref rid="bib52" ref-type="ref">1995b</xref>) and improved the therapeutic efficacy of acyclovir in mice infected with HSV‐1 (Kurokawa <italic>et al.</italic>, <xref rid="bib49" ref-type="ref">1995a</xref>).</p><p>Subsequently, Nakano <italic>et al.</italic> (<xref rid="bib65" ref-type="ref">1998</xref>) also investigated the efficacy of <italic>Rhus chinensis</italic> extract <italic>in vivo, </italic>using a guinea‐pig primarily infected intravaginally with HSV‐2. Prophylactic oral administration of <italic>Rhus chinensis</italic> at the dose corresponding to human use significantly reduced the incidence and severity of spontaneous skin lesions compared with latently infected guinea‐pigs administered water. When recurrent HSV‐2 infection was induced by ultraviolet irradiation 3 months after primary infection, prophylaxis with <italic>Rhus chinensis</italic> was also significantly effective in reducing the severity of ultraviolet‐induced skin lesions.</p><p>Two terpene compounds, moronic acid [<bold>8</bold>] and betulonic acid [<bold>9</bold>], were separated from <italic>Rhus chinensis</italic> and their subsequent anti‐HSV activities were assessed <italic>in vitro</italic> and <italic>in vivo</italic> (Kurokawa <italic>et al.</italic>, <xref rid="bib48" ref-type="ref">1998</xref>). The effective concentrations of moronic acid and betulonic acid for 50% plaque reduction for HSV‐1 were consecutively, 3.9 and 2.6 µg/mL. The therapeutic index of moronic acid (10.3–16.3) was larger than that of betulonic acid (6.2). Oral administration of moronic acid thrice a day to mice infected cutaneously with HSV‐1, significantly retarded the development of skin lesions and/or prolonged the mean survival of infected mice without toxicity compared with the control. Moronic acid exerted stronger anti‐HSV‐1 activity in the brain of HSV‐1‐infected mice than in the skin, similar to the hot‐water extract of <italic>Rhus chinensis </italic>(Kurokawa <italic>et al.</italic>, <xref rid="bib49" ref-type="ref">1995a</xref>, <xref rid="bib48" ref-type="ref">1998</xref>).</p></sec><sec id="sec3-3"><title>Anti‐HCV and anti‐SARS‐CoV activities.</title><p>Screening a library of traditional medicines, Duan <italic>et al.</italic> (<xref rid="bib23" ref-type="ref">2004</xref>) found that the EtOAc extract fraction from <italic>Galla chinensis</italic> was efficient in inhibiting the NS3 protease activity of hepatitis carcinoma virus (HCV). 1,2,6‐Tri‐O‐galloyl‐β‐d‐glucose, 1,2,3,6‐tetra‐O‐galloyl‐β‐d‐glucose and pentagalloylglucose [<bold>1</bold>] were identified as the active compounds. Tri‐, tetra‐ and pentagalloylglucose inhibited HCV NS3 protease with IC<sub>50 </sub>of 1.89, 0.75 and 1.60 µm, respectively (Duan <italic>et al.</italic>, <xref rid="bib23" ref-type="ref">2004</xref>).</p><p>Likewise, tetra‐<italic>O</italic>‐galloyl‐β‐d‐glucose isolated from <italic>Galla chinensis</italic> exhibited prominent inhibition against severe acute respiratory syndrome coronavirus (SARS‐CoV) with a 50% effective concentration of 4.5 µm (Yi et al., <xref rid="bib103" ref-type="ref">2004</xref>).</p></sec></sec><sec id="sec2-3"><title>Anticariogenic activity</title><p>Liu <italic>et al.</italic> (<xref rid="bib60" ref-type="ref">2003</xref>) found that crude aqueous extract of <italic>Galla chinensis</italic> has the ability to inhibit enamel demineralization <italic>in vitro</italic>. In another study, Chu <italic>et al.</italic> (<xref rid="bib21" ref-type="ref">2007</xref>) evaluated the effects of compounds from <italic>Galla chinensis</italic> on the remineralization of initial enamel carious lesions using an <italic>in vitro</italic> pH cycling model. The group demonstrated the potential of three different fractions of <italic>Galla chinensis</italic> to affect net rehardening of artificial carious lesions under dynamic pH‐cyclic conditions. Furthermore, Zou <italic>et al.</italic> (<xref rid="bib109" ref-type="ref">2008</xref>), using the same protocol, demonstrated the potential of <italic>Galla chinensis</italic> extract to inhibit the demineralization of initial enamel carious lesions.</p><p>The chemical compounds of <italic>Galla chinensis</italic> showed effects and combined effects with fluoride on enhancing remineralization of dental enamel (Cheng et al., <xref rid="bib16" ref-type="ref">2008</xref>).</p><p>At this point, the active compound of <italic>Galla chinensis</italic> involved in remineralization or demineralization is still unknown. Chu <italic>et al.</italic> (<xref rid="bib21" ref-type="ref">2007</xref>) isolated gallic acid [<bold>2</bold>] and methyl gallate [<bold>3</bold>], both of which showed poor activity compared with the crude extract. This result was confirmed by Cheng <italic>et al.</italic> (<xref rid="bib16" ref-type="ref">2008</xref>) testing the combined effects of <italic>Galla chinensis</italic> extract or gallic acid with fluoride on remineralization of artificial early enamel caries. They found that both the crude extract of <italic>Galla chinensis</italic> and gallic acid had synergistic effects with fluoride on remineralization, but with apparent differing mechanisms. Thus, it seemed that gallic acid was not the only possible active constituent of <italic>Galla chinensis</italic> to enhance remineralization. Zou <italic>et al.</italic> (<xref rid="bib109" ref-type="ref">2008</xref>) similarly attempted to determine which of the constituent chemical fractions of <italic>Galla </italic>chinensis conferred a potential anticaries benefit by comparing the effects of four different fractions of <italic>Galla chinensis</italic> on demineralization of a bovine enamel model. The crude extract was the most active one, prone to some losses of other active compounds during the separation process.</p></sec><sec id="sec2-4"><title>Antioxidant activity</title><p>Cai <italic>et al.</italic> (<xref rid="bib12" ref-type="ref">2004</xref>) screened 112 Chinese medicinal plants for antioxidant activity; the results showed that the aqueous extract of <italic>Galla chinensis</italic> contained the highest antioxidant concentration of 17674 µmol TEAC/100 g.</p><p>More recently, two similar studies have investigated the antioxidant activity of gallotannins in four different systems, namely 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power, β‐carotene linoleic acid system and hydroxyl radical scavenging assays. Tian <italic>et al.</italic> (<xref rid="bib89" ref-type="ref">2009a</xref>) tested the antioxidant activity of gallotannins with different polarities and found that all of the consecutive extracts of <italic>Galla chinensis</italic> possessed remarkable antioxidant activity. For example, DPPH radical scavenging activity, EC<sub>50</sub> were in the sequence ethyl acetate (1.22 µg/mL) > ether (1.44 µg/mL) > ethanol (1.55 µg/mL) > water (2.11 µg/mL). Generally, all fractions showed better capacity to scavenge free radicals than the controls, BHT and TROLOX. The same results trend was observed with ferric reducing activity. Antioxidant activity increased when the polarity of extracts decreased, suggesting that extracts with weaker polarities contained higher molecular weight tannins, and thus had stronger antioxidant effects. Aware of this finding, (Tian et al. <xref rid="bib90" ref-type="ref">2009b</xref>) isolated different gallotannins, containing 1–10 galloylglucoses (GG), from <italic>Galla chinensis</italic> and investigated their antioxidant activities in the above systems. Generally, gallotannins of high degrees of galloylation (5–10 GGs) had stronger antioxidant activities than those of low degrees of galloylation (1–4 GGs).The same conclusion was drawn in earlier work by Yokozawa <italic>et al.</italic> (<xref rid="bib104" ref-type="ref">1998</xref>).</p><p>Similarly, methyl gallate and gallic acid have been shown through <italic>in vivo </italic>and <italic>in vitro </italic>studies to have antioxidant and radical scavenging activity (Chen and Zhang, <xref rid="bib13" ref-type="ref">2003</xref>; Whang <italic>et al.</italic>, <xref rid="bib96" ref-type="ref">2005</xref>; Madsen and Bertelsen, <xref rid="bib61" ref-type="ref">1995</xref>; Peyrat‐Maillard <italic>et al.</italic>, <xref rid="bib78" ref-type="ref">2000</xref>).</p><p>It has been demonstrated that pentagalloylglucose possesses antioxidant activity and protects rat neuronal cells from oxidative damage (Choi <italic>et al.</italic>, <xref rid="bib17" ref-type="ref">2002</xref>; Feldman et al., <xref rid="bib25" ref-type="ref">2001</xref>; Oh <italic>et al.</italic>, <xref rid="bib68" ref-type="ref">2001</xref>; Pan <italic>et al.</italic>, <xref rid="bib72" ref-type="ref">1999</xref>). Piao <italic>et al.</italic> (<xref rid="bib79" ref-type="ref">2009</xref>) showed that pentagalloylglucose exerts antiapoptotic activity through antioxidant properties.</p></sec><sec id="sec2-5"><title>Anticancer activity</title><p>Yang <italic>et al.</italic> (<xref rid="bib101" ref-type="ref">2005</xref>) were the first to report the anticancer activity of <italic>Rhus chinensis</italic> extract on carcinogenic Cdc25 phosphatases. Several molecules found in <italic>Rhus chinensis</italic> such as pentagalloylglucose and gallic acid have been shown to have anticancer activity (Bhimani <italic>et al.</italic>, <xref rid="bib9" ref-type="ref">1993</xref>; Madsen and Bertelsen, <xref rid="bib61" ref-type="ref">1995</xref>; Chung <italic>et al.</italic>, <xref rid="bib22" ref-type="ref">1998</xref>; Hu <italic>et al.</italic>, <xref rid="bib34" ref-type="ref">2008</xref>; Kuo <italic>et al.</italic>, <xref rid="bib47" ref-type="ref">2009</xref>). Pentagalloylglucose has been shown to exhibit <italic>in vivo</italic> anticancer effects against prostate cancer (Hu <italic>et al.</italic>, <xref rid="bib34" ref-type="ref">2008</xref>; Kuo <italic>et al.</italic>, <xref rid="bib47" ref-type="ref">2009</xref>), lung cancer (Huh <italic>et al.</italic>, <xref rid="bib35" ref-type="ref">2005</xref>) and sarcoma (Miyamoto <italic>et al.</italic>, <xref rid="bib64" ref-type="ref">1987</xref>), and <italic>in vitro</italic> inhibitory effects on the growth and/or invasion of breast cancer, leukemia, melanoma and liver cancer (Zhang <italic>et al.</italic>, <xref rid="bib105" ref-type="ref">2009</xref>). Pentagalloylglucose can exert anticancer activity via the inhibition of angiogenesis (Lee <italic>et al.</italic>, <xref rid="bib55" ref-type="ref">2004</xref>; Huh <italic>et al.</italic>, <xref rid="bib35" ref-type="ref">2005</xref>) and invasion of melanoma cells in metastasis (Ho <italic>et al.</italic>, <xref rid="bib31" ref-type="ref">2002</xref>). <italic>In vitro</italic> studies showed that pentagalloylglucose significantly inhibited the proliferation and tube formation of bFGF‐treated human umbilical vein endothelial cells (HUVEC) with an IC<sub>50</sub> of 8 µm (Huh <italic>et al.</italic>, <xref rid="bib35" ref-type="ref">2005</xref>). The result is similar to the <italic>in vitro</italic> antiangiogenic activity of pentagalloylglucose in VEGF‐treated HUVECs (Lee <italic>et al.</italic>, <xref rid="bib55" ref-type="ref">2004</xref>). Daily injection of 4 and 20 mg/kg of pentagalloylglucose significantly inhibited the growth of the highly angiogenesis‐dependent Lewis Lung Cancer allograft by 57% and 91%, respectively (Huh <italic>et al.</italic>, <xref rid="bib35" ref-type="ref">2005</xref>). Similarly, pentagalloylglucose inhibited the invasion of highly metastatic mouse melanoma B16F10 cells <italic>in vitro</italic> in a dose‐ and time‐dependent manner, with IC<sub>50</sub> of 15 µm (Ho <italic>et al.</italic>, <xref rid="bib31" ref-type="ref">2002</xref>).</p><p>Some other investigations have also demonstrated that derivatives of galloylglucose inhibit not only cancer cell growth (Pan <italic>et al.</italic>, <xref rid="bib72" ref-type="ref">1999</xref>; Hu <italic>et al.</italic>, <xref rid="bib34" ref-type="ref">2008</xref>) but also the invasion of HT1080 human fibrosarcoma cells (Ata <italic>et al.</italic>, <xref rid="bib6" ref-type="ref">1996</xref>).</p></sec><sec id="sec2-6"><title>Hepatoprotective activity</title><p>Several studies of natural hepatoprotective agents have revealed that the extract of <italic>Galla chinensis</italic> showed promising hepatoprotective activity (Oh <italic>et al.</italic>, <xref rid="bib69" ref-type="ref">2002</xref>; Tian <italic>et al.</italic>, <xref rid="bib91" ref-type="ref">2005</xref>). Based on an activity‐guided separation scheme An <italic>et al.</italic> (<xref rid="bib5" ref-type="ref">2005</xref>) purified pentagalloylglucose [<bold>1</bold>] and an equilibrium mixture of 3‐galloyl‐gallic acid and 4‐galloyl‐gallic acid isomer from the methanol extract of <italic>Galla chinensis</italic> and validated their hepatoprotective activity. Pentagalloylglucose [<bold>1</bold>] and the mixture compounds were found to have marked protective effects on tacrine‐induced cytotoxicity in human liver‐derived Hep G2 cells with EC<sub>50</sub> values of 70.39 ± 5.4 and 29.51 ± 0.7 µm, respectively, and also inhibited nitrofurantoin‐induced cytotoxicity in Hep G2 cells at 150.9 ± 6.4 and 23.81 ± 0.5 µm respectively.</p><p>Furthermore, pentagalloylglucose treatment was able to reduce both hepatocyte necrosis induced by tert‐butyl hydroperoxide (4 and 20 µm) and apoptosis induced by glycochenodeoxycholic acid (3.125 to 50 µm) in primary rat hepatocytes (Park <italic>et al.</italic>, <xref rid="bib74" ref-type="ref">2008</xref>).</p></sec><sec id="sec2-7"><title>Antidiabetic activity</title><p>Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose level due to agents such as α‐glucosidase enzyme, which boosts the digestion of carbohydrate to monosaccharides in the process of intestinal absorption.</p><p>Therefore, Shim <italic>et al.</italic> (<xref rid="bib84" ref-type="ref">2003</xref>) tested the inhibitory effect of an aqueous extract from the gall of <italic>Rhus chinensis</italic> on α‐glucosidase activity in <italic>in vitro</italic> and <italic>in vivo</italic> models. <italic>Galla chinensis</italic> inhibited <italic>Bacillus</italic> α‐glucosidase activity with an IC<sub>50</sub> of 0.9 µg/mL. Its inhibition on α‐glucosidase was determined to be noncompetitive and reversible when the enzyme–substrate mixture was simultaneously treated with <italic>Galla chinensis</italic>. <italic>Galla chinensis</italic> significantly suppressed the increase of blood glucose level in rats after oral administration of sucrose. These results suggest that <italic>Galla chinensis</italic> might exert antidiabetic effects by suppressing carbohydrate absorption from the intestine and thereby reducing the postprandial increase in the blood glucose.</p><p>Likewise, tannic acid, a mixture of gallotannins containing pentagalloylglucose, was found to have a hypoglycemic effect in patients with type 2 diabetes (Gin <italic>et al.</italic>, <xref rid="bib28" ref-type="ref">1999</xref>). Aware of this result, Li and coworkers hypothesized that pentagalloylglucose could have antidiabetic activity. Using synthetic pentagalloylglucose <italic>in vitro</italic> and in an animal assay, it was demonstrated that pentagalloylglucose effectively reduced blood glucose and insulin levels <italic>in vitro</italic> and in animal models (Li <italic>et al.</italic>, <xref rid="bib58" ref-type="ref">2005</xref>). Unlike most antidiabetic drugs, pentagalloylglucose may reduce blood glucose without increasing adiposity.</p></sec><sec id="sec2-8"><title>Antidiarrheal activity</title><p>The methanol extract of the dried ripe fruit of <italic>Rhus chinensis</italic> was tested in experimental models of castor oil‐induced diarrhea in Swiss albino mice (Tangpu and Yadav, <xref rid="bib87" ref-type="ref">2004</xref>; Bose <italic>et al.</italic>, <xref rid="bib10" ref-type="ref">2008</xref>). At graded doses, the extract showed remarkable antidiarrheal activity evidenced by an 80.70% reduction in the rate of defecation of control animals at a dose of 600 mg/kg body weight. The extract also reduced intestinal fluid secretion induced by MgSO<sub>4</sub> and gastrointestinal motility after charcoal meal administration in albino mice (Tangpu and Yadav, <xref rid="bib87" ref-type="ref">2004</xref>).</p><p>In the same way, <italic>Galla chinensis</italic> extracts were found to be effective against enterotoxigenic <italic>Escherichia coli</italic>‐induced diarrhea that produces a heat‐labile enterotoxin (LT), which binds to the ganglioside G<sub>M1</sub> on the surface of intestinal epithelial cells (Holmgren and Svennerholm, <xref rid="bib33" ref-type="ref">1992</xref>) leading to a massive loss of fluids and ions from cells (Chen <italic>et al.</italic>, <xref rid="bib15" ref-type="ref">2009</xref>). Using the patent mouse gut assay <italic>in vivo</italic> study, Chen <italic>et al.</italic> (<xref rid="bib14" ref-type="ref">2006</xref>) found that <italic>Galla chinensis</italic> extract exhibited an anti‐LT‐induced diarrheal effect, with an IC<sub>50</sub> value of 4.7 ± 1.3 mg/mL. Competitive GM1‐ELISA assay showed that <italic>Galla chinensis</italic> suppressed (IC<sub>50</sub> = 0.17 ± 0.02 mg/mL) LT‐induced fluid accumulation by blocking the binding of LTB to G<sub>M1</sub>. Thin layer chromatography suggests that the most active fraction that inhibited the binding of LTB to GM1 was composed of mainly phenolics, especially gallic acid which significantly blocked the binding of LTB to G<sub>M1</sub>, with an IC<sub>50</sub> value of 10.9 ± 0.3 mm, and suppressed the LT‐induced fluid accumulation in a dose‐dependent manner, with an IC<sub>50</sub> value of 25.4 ± 11.6 mm.</p></sec><sec id="sec2-9"><title>Antiinflammatory and antithrombin activities</title><p>The work of Kim <italic>et al.</italic> (<xref rid="bib45" ref-type="ref">2005</xref>) showed that <italic>Galla chinensis</italic> had antiinflammatory activity in <italic>in vivo</italic> and <italic>in vitro</italic> models. <italic>Galla chinensis </italic>could control all of the inflammatory mediators, such as histamine, heparin, lipid‐derived mediators and various cytokines in the model of immediate‐type allergic reaction in a dose‐dependent manner through different mechanisms. Latter activity‐guided fractionation and purification of the EtOAc fractions of the <italic>Galla chinensis</italic> indicated that the main antiallergic component in <italic>Galla chinensis</italic> was gallic acid.</p><p>Fisetin a flavonoid found in the root of <italic>Rhus chinensis</italic> (Lin <italic>et al.</italic>, <xref rid="bib59" ref-type="ref">2008</xref>) was also found to down‐regulate inflammatory reactions in stimulated human mast cells (Park <italic>et al.</italic>, <xref rid="bib73" ref-type="ref">2007</xref>).</p><p>Similarly, pentagalloylglucose has been shown through <italic>in vivo </italic>and <italic>in vitro </italic>studies to exercise a strong antiinflammatory effect (Oh <italic>et al.</italic>, <xref rid="bib67" ref-type="ref">2004</xref>; Lee <italic>et al.</italic>, <xref rid="bib54" ref-type="ref">2007</xref>, <xref rid="bib56" ref-type="ref">2003</xref>; Kang <italic>et al.</italic>, <xref rid="bib38" ref-type="ref">2005</xref>).</p><p>6‐Pentadecylsalicylic acid has been isolated from air‐dried stems of <italic>Rhus chinensis</italic> by bioassay‐directed fractionation of the <italic>n</italic>‐hexane extract of the stem (Kuo, 1991). This compound showed antithrombotic activity at 50 µg/mL using the amidolytic method (Kuo, 1991). It also prolonged clotting time in a dose‐dependent manner in the clotting assay of thrombin–fibrinogen interaction.<xref rid="fig1" ref-type="fig">1</xref></p><fig fig-type="Figure" xml:lang="en" id="fig1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Structures of selected phytochemicals from <italic>Rhus chinensis</italic> and <italic>Galla chinensis</italic>: pentagalloylglucose [<bold>1</bold>], gallic acid [<bold>2</bold>], methyl gallate [<bold>3</bold>], 5‐hydroxy‐3‐(propan‐2‐ylidene)‐7‐(3,7,11,15‐tetramethylhexade‐ca‐2,6,10,11‐tetraenyl)‐2(3H)‐benzofuranone [<bold>4</bold>], 5‐hydroxy‐7‐(3,7,11,15‐tetramethylhexadeca‐2,6,10,11‐tetraenyl)‐2(3H)‐benzofuranone [<bold>5</bold>], 3‐oxo‐6β‐hydroxyolean‐12‐en‐28‐oic acid [<bold>6</bold>], 3‐oxo‐6β‐hydroxyolean‐18‐en‐28‐oic acid [<bold>7</bold>], moronic acid [<bold>8</bold>],betulonic acid [<bold>9</bold>], gallicin [<bold>10</bold>], dihydroxytoluene [<bold>11</bold>], dimethylcaffic acid [<bold>12</bold>], fisetin [<bold>13</bold>], 6‐pentadecylsalicylic acid [<bold>14</bold>].</p></caption><graphic id="nlm-graphic-1" xlink:href="PTR-24-1739-g001"><permissions><copyright-holder>John Wiley & Sons, Ltd.</copyright-holder><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions></graphic></fig></sec></sec><sec id="sec1-5"><title>CONCLUSIONS</title><p><italic>Rhus chinensis</italic> species have long been recognized by folk medicine practitioners as having value and have been revealed to have great medicinal potential, much of which was completely unknown to Western scientists. Over the past few decades, the research efforts on <italic>Rhus chinensis</italic> extracts indicate that the extracts have promising potential as antiviral, anticarie, antidiarrheal, anticancer, antidiabetic and hepatoprotective agents, among others. Although the work reviewed here substantiated most of the traditional claims on its health effectiveness, more research is required for validation of the uses of this plant.</p><p>The available information on the different bioactive contents in samples of various parts of this medicinal plant is very limited, both qualitatively and quantitatively. The gall on <italic>Rhus chinensis</italic> leaves has received much scientific attention because of its high gallotannin content and subsequent health potential. However, other parts, such as fruits, leaves, and seeds, can also be investigated based on traditional uses and the findings in other <italic>Rhus</italic> species.</p><p>So far, <italic>Galla chinensis</italic> is the only medicine proven to remineralize a hard tissue like enamel. This is a unique potential for this plant, but the active constituent is still unknown.</p><p>The mechanistic activity of <italic>Rhus chinensis</italic> material as prophylactic, therapeutic, anti‐HSV, anti‐HIV and anti‐diarrheal medicine needs to be further examined. On the other hand, efforts should also be made to survey other sumac species to determine if these properties are generalized across the <italic>Rhus</italic> genus.</p><p>The safety of <italic>Rhus chinensis</italic> still needs to be rigorously established, since cases of toxicity from intake of gallotannins found in <italic>Rhus chinensis</italic> have been reported in the literature. Different gallotannins such as tri‐, tetra‐, hexa‐, hepta‐, octa‐, nona‐ and decagalloylglucose can reduce blood pressure and blood urea nitrogen, as reported in animal studies in the literature (Feldman <italic>et al.</italic>, <xref rid="bib26" ref-type="ref">1999</xref>; Hofmann <italic>et al.</italic>, <xref rid="bib32" ref-type="ref">2006</xref>; Nishizawa <italic>et al.</italic>, <xref rid="bib66" ref-type="ref">1983</xref>). Nonetheless, tannins diminish protein digestibility when present in high levels in diets with low protein content and also inhibit human salivary α‐amylase, thereby causing potential negative effects on starch digestion and food taste. This needs to be taken in account when testing the efficacy of <italic>Rhus chinensis</italic> compounds in human beings by clinical trials for drug use validation.</p></sec></body><back><ack id="sec1-ack-1"><title>Acknowledgements</title><p>Support was provided by the Chinese government research funds of 111 project‐B07029, PCSIRT0627 and 2008BAD91B04‐2.</p></ack><ref-list><title>REFERENCES</title><ref id="bib1"><mixed-citation publication-type="journal" id="cit1"><string-name><surname>Abbasi</surname><given-names>AM</given-names></string-name>, <string-name><surname>Khan</surname><given-names>MA</given-names></string-name>, <string-name><surname>Ahmad</surname><given-names>M</given-names></string-name><italic>et al</italic><year>2009</year><article-title>Medicinal plants used for the treatment of jaundice and hepatitis based on socio‐economic documentation</article-title>. <source xml:lang="en">Afr J Biotechnol</source><volume>8</volume>: <fpage>1643</fpage>–<lpage>1650</lpage>.
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