Epimedium koreanum Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus In Vitro and In Vivo
Identifieur interne : 000774 ( Pmc/Checkpoint ); précédent : 000773; suivant : 000775Epimedium koreanum Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus In Vitro and In Vivo
Auteurs : Won-Kyung Cho [Corée du Sud] ; Hyunil Kim [Corée du Sud] ; Yu Jeong Choi [Corée du Sud] ; Nam-Hui Yim [Corée du Sud] ; Hye Jin Yang [Corée du Sud] ; Jin Yeul Ma [Corée du Sud]Source :
- Evidence-based Complementary and Alternative Medicine : eCAM [ 1741-427X ] ; 2012.
Abstract
Porcine epidemic diarrhea virus (PEDV) causes diarrhea of pigs age-independently and death of young piglets, resulting in economic loss of porcine industry. We have screened 333 natural oriental herbal medicines to search for new antiviral candidates against PEDV. We found that two herbal extracts, KIOM 198 and KIOM 124, contain significant anti-PED viral effect. KIOM 198 and KIOM 124 were identified as
Url:
DOI: 10.1155/2012/985151
PubMed: 23259003
PubMed Central: 3521454
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>Epimedium koreanum</italic> Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus <italic>In Vitro</italic> and <italic>In Vivo</italic></title><author><name sortKey="Cho, Won Kyung" sort="Cho, Won Kyung" uniqKey="Cho W" first="Won-Kyung" last="Cho">Won-Kyung Cho</name><affiliation wicri:level="1"><nlm:aff id="I1">Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811</wicri:regionArea><wicri:noRegion>Daejeon 305-811</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Hyunil" sort="Kim, Hyunil" uniqKey="Kim H" first="Hyunil" last="Kim">Hyunil Kim</name><affiliation wicri:level="1"><nlm:aff id="I2">Optifarm Solution, 48 Songnam-ri, Seonggeo-eup, Seobuk-gu, Cheonan-si 331-834, Chungcheongnam-do, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Optifarm Solution, 48 Songnam-ri, Seonggeo-eup, Seobuk-gu, Cheonan-si 331-834, Chungcheongnam-do</wicri:regionArea><wicri:noRegion>Chungcheongnam-do</wicri:noRegion></affiliation></author><author><name sortKey="Choi, Yu Jeong" sort="Choi, Yu Jeong" uniqKey="Choi Y" first="Yu Jeong" last="Choi">Yu Jeong Choi</name><affiliation wicri:level="1"><nlm:aff id="I2">Optifarm Solution, 48 Songnam-ri, Seonggeo-eup, Seobuk-gu, Cheonan-si 331-834, Chungcheongnam-do, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Optifarm Solution, 48 Songnam-ri, Seonggeo-eup, Seobuk-gu, Cheonan-si 331-834, Chungcheongnam-do</wicri:regionArea><wicri:noRegion>Chungcheongnam-do</wicri:noRegion></affiliation></author><author><name sortKey="Yim, Nam Hui" sort="Yim, Nam Hui" uniqKey="Yim N" first="Nam-Hui" last="Yim">Nam-Hui Yim</name><affiliation wicri:level="1"><nlm:aff id="I1">Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811</wicri:regionArea><wicri:noRegion>Daejeon 305-811</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Hye Jin" sort="Yang, Hye Jin" uniqKey="Yang H" first="Hye Jin" last="Yang">Hye Jin Yang</name><affiliation wicri:level="1"><nlm:aff id="I1">Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811</wicri:regionArea><wicri:noRegion>Daejeon 305-811</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Jin Yeul" sort="Ma, Jin Yeul" uniqKey="Ma J" first="Jin Yeul" last="Ma">Jin Yeul Ma</name><affiliation wicri:level="1"><nlm:aff id="I1">Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811</wicri:regionArea><wicri:noRegion>Daejeon 305-811</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23259003</idno><idno type="pmc">3521454</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521454</idno><idno type="RBID">PMC:3521454</idno><idno type="doi">10.1155/2012/985151</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000853</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000853</idno><idno type="wicri:Area/Pmc/Curation">000853</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000853</idno><idno type="wicri:Area/Pmc/Checkpoint">000774</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000774</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>Epimedium koreanum</italic> Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus <italic>In Vitro</italic> and <italic>In Vivo</italic></title><author><name sortKey="Cho, Won Kyung" sort="Cho, Won Kyung" uniqKey="Cho W" first="Won-Kyung" last="Cho">Won-Kyung Cho</name><affiliation wicri:level="1"><nlm:aff id="I1">Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811</wicri:regionArea><wicri:noRegion>Daejeon 305-811</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Hyunil" sort="Kim, Hyunil" uniqKey="Kim H" first="Hyunil" last="Kim">Hyunil Kim</name><affiliation wicri:level="1"><nlm:aff id="I2">Optifarm Solution, 48 Songnam-ri, Seonggeo-eup, Seobuk-gu, Cheonan-si 331-834, Chungcheongnam-do, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Optifarm Solution, 48 Songnam-ri, Seonggeo-eup, Seobuk-gu, Cheonan-si 331-834, Chungcheongnam-do</wicri:regionArea><wicri:noRegion>Chungcheongnam-do</wicri:noRegion></affiliation></author><author><name sortKey="Choi, Yu Jeong" sort="Choi, Yu Jeong" uniqKey="Choi Y" first="Yu Jeong" last="Choi">Yu Jeong Choi</name><affiliation wicri:level="1"><nlm:aff id="I2">Optifarm Solution, 48 Songnam-ri, Seonggeo-eup, Seobuk-gu, Cheonan-si 331-834, Chungcheongnam-do, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Optifarm Solution, 48 Songnam-ri, Seonggeo-eup, Seobuk-gu, Cheonan-si 331-834, Chungcheongnam-do</wicri:regionArea><wicri:noRegion>Chungcheongnam-do</wicri:noRegion></affiliation></author><author><name sortKey="Yim, Nam Hui" sort="Yim, Nam Hui" uniqKey="Yim N" first="Nam-Hui" last="Yim">Nam-Hui Yim</name><affiliation wicri:level="1"><nlm:aff id="I1">Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811</wicri:regionArea><wicri:noRegion>Daejeon 305-811</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Hye Jin" sort="Yang, Hye Jin" uniqKey="Yang H" first="Hye Jin" last="Yang">Hye Jin Yang</name><affiliation wicri:level="1"><nlm:aff id="I1">Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811</wicri:regionArea><wicri:noRegion>Daejeon 305-811</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Jin Yeul" sort="Ma, Jin Yeul" uniqKey="Ma J" first="Jin Yeul" last="Ma">Jin Yeul Ma</name><affiliation wicri:level="1"><nlm:aff id="I1">Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811</wicri:regionArea><wicri:noRegion>Daejeon 305-811</wicri:noRegion></affiliation></author></analytic><series><title level="j">Evidence-based Complementary and Alternative Medicine : eCAM</title><idno type="ISSN">1741-427X</idno><idno type="eISSN">1741-4288</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Porcine epidemic diarrhea virus (PEDV) causes diarrhea of pigs age-independently and death of young piglets, resulting in economic loss of porcine industry. We have screened 333 natural oriental herbal medicines to search for new antiviral candidates against PEDV. We found that two herbal extracts, KIOM 198 and KIOM 124, contain significant anti-PED viral effect. KIOM 198 and KIOM 124 were identified as <italic>Epimedium koreanum</italic> Nakai and <italic>Lonicera japonica</italic> Thunberg, respectively. The further plaque and CPE inhibition assay <italic>in vitro</italic> showed that KIOM 198 has much stronger antiviral activity than KIOM 124. Additionally, KIOM 198 exhibited a similar extent of antiviral effect against other subtypes of Corona virus such as sm98 and TGE viruses. Cytotoxicity results showed that KIOM 198 is nontoxic on the cells and suggest that it can be delivered safely for therapy. Furthermore, when we orally administered KIOM 198 to piglets and then infected them with PEDV, the piglets did not show any disease symptoms like diarrhea and biopsy results showed clean intestine, whereas control pigs without KIOM 198 treatment exhibited PED-related severe symptoms. These results imply that KIOM 198 contains strong antiviral activity and has a potential to be developed as an antiviral phytomedicine to treat PEDV-related diseases in pigs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Debouck, P" uniqKey="Debouck P">P Debouck</name></author><author><name sortKey="Pensaert, M" uniqKey="Pensaert M">M Pensaert</name></author><author><name sortKey="Coussement, W" uniqKey="Coussement W">W Coussement</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pensaert, Mb" uniqKey="Pensaert M">MB Pensaert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Debouck, P" uniqKey="Debouck P">P Debouck</name></author><author><name sortKey="Pensaert, M" uniqKey="Pensaert M">M Pensaert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ducatelle, R" uniqKey="Ducatelle R">R Ducatelle</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Evid Based Complement Alternat Med</journal-id><journal-id journal-id-type="iso-abbrev">Evid Based Complement Alternat Med</journal-id><journal-id journal-id-type="publisher-id">ECAM</journal-id><journal-title-group><journal-title>Evidence-based Complementary and Alternative Medicine : eCAM</journal-title></journal-title-group><issn pub-type="ppub">1741-427X</issn><issn pub-type="epub">1741-4288</issn><publisher><publisher-name>Hindawi Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23259003</article-id><article-id pub-id-type="pmc">3521454</article-id><article-id pub-id-type="doi">10.1155/2012/985151</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title><italic>Epimedium koreanum</italic> Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus <italic>In Vitro</italic> and <italic>In Vivo</italic></article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Cho</surname><given-names>Won-Kyung</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Hyunil</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Choi</surname><given-names>Yu Jeong</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yim</surname><given-names>Nam-Hui</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Hye Jin</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ma</surname><given-names>Jin Yeul</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="I1"><sup>1</sup>Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon 305-811, Republic of Korea</aff><aff id="I2"><sup>2</sup>Optifarm Solution, 48 Songnam-ri, Seonggeo-eup, Seobuk-gu, Cheonan-si 331-834, Chungcheongnam-do, Republic of Korea</aff><author-notes><corresp id="cor1">*Jin Yeul Ma: <email>jyma@kiom.re.kr</email></corresp><fn fn-type="other"><p>Academic Editor: Virginia S. Martino</p></fn></author-notes><pub-date pub-type="ppub"><year>2012</year></pub-date><pub-date pub-type="epub"><day>29</day><month>11</month><year>2012</year></pub-date><volume>2012</volume><elocation-id>985151</elocation-id><history><date date-type="received"><day>18</day><month>5</month><year>2012</year></date><date date-type="rev-recd"><day>19</day><month>10</month><year>2012</year></date><date date-type="accepted"><day>6</day><month>11</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012 Won-Kyung Cho et al.</copyright-statement><copyright-year>2012</copyright-year><license xlink:href="https://creativecommons.org/licenses/by/3.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Porcine epidemic diarrhea virus (PEDV) causes diarrhea of pigs age-independently and death of young piglets, resulting in economic loss of porcine industry. We have screened 333 natural oriental herbal medicines to search for new antiviral candidates against PEDV. We found that two herbal extracts, KIOM 198 and KIOM 124, contain significant anti-PED viral effect. KIOM 198 and KIOM 124 were identified as <italic>Epimedium koreanum</italic> Nakai and <italic>Lonicera japonica</italic> Thunberg, respectively. The further plaque and CPE inhibition assay <italic>in vitro</italic> showed that KIOM 198 has much stronger antiviral activity than KIOM 124. Additionally, KIOM 198 exhibited a similar extent of antiviral effect against other subtypes of Corona virus such as sm98 and TGE viruses. Cytotoxicity results showed that KIOM 198 is nontoxic on the cells and suggest that it can be delivered safely for therapy. Furthermore, when we orally administered KIOM 198 to piglets and then infected them with PEDV, the piglets did not show any disease symptoms like diarrhea and biopsy results showed clean intestine, whereas control pigs without KIOM 198 treatment exhibited PED-related severe symptoms. These results imply that KIOM 198 contains strong antiviral activity and has a potential to be developed as an antiviral phytomedicine to treat PEDV-related diseases in pigs.</p></abstract></article-meta></front><floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>The antiviral activities of KIOM 124 and KIOM 198 on PED virus. The Vero cells were infected with 0.1 MOI of PEDV for 1 h and followed by adding 20-fold diluted herbal extract containing KIOM 124 (a) or KIOM 198 (b), and further incubated for 48 h or 72 h.</p></caption><graphic xlink:href="ECAM2012-985151.001"></graphic></fig><fig id="fig2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Effect of KIOM 124 and KIOM 198 on viral propagation. Cells infected with 0.1 MOI of virus were further incubated with 20-fold diluted KIOM 124 or KIOM 198 herbal extract. At 18 h, 24 h, and 48 h postinfection, each supernatant was collected and serially diluted for titration. Total viral titers were determined as a plaque forming unit (PFU). (a) Time-course kinetics of virus replicated in the presence or absence of KIOM 124 or KIOM 198 herbal extract. (b) The cells and plaques stained with crystal violet in the presence of KIOM 124 or KIOM 198.</p></caption><graphic xlink:href="ECAM2012-985151.002"></graphic></fig><fig id="fig3" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Antiviral effect of KIOM 198 on corona virus other subtype sm98 virus and TGE virus. (a) The Vero cells were infected with sm98 virus at an MOI of 0.01 for 1 h and added with 20-fold diluted KIOM 198 extract, and further incubated for 24 h, 48 h, and 72 h. (b) TGE virus at an MOI of 0.01 was used to infect ST-cells and incubated with KIOM 198 for 24 h.</p></caption><graphic xlink:href="ECAM2012-985151.003"></graphic></fig><fig id="fig4" orientation="portrait" position="float"><label>Figure 4</label><caption><p> (a) Cytotoxicity of herbal extract containing antiviral activity in Vero cells. The 27 different herbal extracts were evaluated to examine toxicity on the cells. (b) Cytotoxicity of KIOM 198 on mouse primary liver cells.</p></caption><graphic xlink:href="ECAM2012-985151.004"></graphic></fig><fig id="fig5" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Effect of KIOM 198 on pigs infected by PED virus. The germ-free piglets were orally injected PED virus after 4 days diet with or without KIOM 198. KIOM 198 extract was added up to 0.6% of diet. After 24 h, the feces of control or KIOM 198-dieted piglets were observed (a). Necropsy was performed to check the intestine of piglet infected with virus in the presence and absence of KIOM 198 (b). After 24 h and 48 h of virus inoculation and at necropsy, the feces were collected to determine viral propagation yield (c).</p></caption><graphic xlink:href="ECAM2012-985151.005"></graphic></fig><fig id="fig6" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Analysis of the component profile of KIOM 198 by RP-HPLC-DAD (run time: 70 min, mobile phase A: water 99.9% + TFA 0.1%, B: Acetonitrile 100%; 10% B (0–5 min), 10–40% B (5–60 min), and 40% (60–70 min), injection: 10 <italic>μ</italic>L, UV wavelength: 270 nm. Several peaks including quercetin (1) and icariin (2) were detected in KIOM 198.</p></caption><graphic xlink:href="ECAM2012-985151.006"></graphic></fig><table-wrap id="tab1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Screening of herbal extract containing antiviral activity against PED virus. 333 herbal extracts were evaluated for the inhibitory effect on PED viral production and 27 herbal extracts having anti-PED viral activity were selected. Antiviral activity was examined by plaque assay and determined as a PFU (plaque forming unit). KIOM 124 and KIOM 198 exhibited strong inhibitory effect on PED viral propagation.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Extract number</th><th align="center" rowspan="1" colspan="1">PEDV-PFU</th><th align="center" rowspan="1" colspan="1">PEDV log PFU</th><th align="center" rowspan="1" colspan="1">Fold inhibition</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">30 </td><td align="center" rowspan="1" colspan="1">713.1</td><td align="center" rowspan="1" colspan="1">2.853</td><td align="center" rowspan="1" colspan="1">410 </td></tr><tr><td align="left" rowspan="1" colspan="1">32 </td><td align="center" rowspan="1" colspan="1">7391</td><td align="center" rowspan="1" colspan="1">3.869</td><td align="center" rowspan="1" colspan="1">40 </td></tr><tr><td align="left" rowspan="1" colspan="1">43 </td><td align="center" rowspan="1" colspan="1">2488</td><td align="center" rowspan="1" colspan="1">3.396</td><td align="center" rowspan="1" colspan="1">118 </td></tr><tr><td align="left" rowspan="1" colspan="1">44 </td><td align="center" rowspan="1" colspan="1">1736</td><td align="center" rowspan="1" colspan="1">3.24</td><td align="center" rowspan="1" colspan="1">168 </td></tr><tr><td align="left" rowspan="1" colspan="1">48 </td><td align="center" rowspan="1" colspan="1">2962</td><td align="center" rowspan="1" colspan="1">3.472</td><td align="center" rowspan="1" colspan="1">99 </td></tr><tr><td align="left" rowspan="1" colspan="1">49 </td><td align="center" rowspan="1" colspan="1">20570</td><td align="center" rowspan="1" colspan="1">4.313</td><td align="center" rowspan="1" colspan="1">14 </td></tr><tr><td align="left" rowspan="1" colspan="1">51 </td><td align="center" rowspan="1" colspan="1">85600</td><td align="center" rowspan="1" colspan="1">4.932</td><td align="center" rowspan="1" colspan="1">3 </td></tr><tr><td align="left" rowspan="1" colspan="1">55 </td><td align="center" rowspan="1" colspan="1">1084</td><td align="center" rowspan="1" colspan="1">3.035</td><td align="center" rowspan="1" colspan="1">270 </td></tr><tr><td align="left" rowspan="1" colspan="1">56 </td><td align="center" rowspan="1" colspan="1">2174</td><td align="center" rowspan="1" colspan="1">3.337</td><td align="center" rowspan="1" colspan="1">135 </td></tr><tr><td align="left" rowspan="1" colspan="1">57 </td><td align="center" rowspan="1" colspan="1">2678</td><td align="center" rowspan="1" colspan="1">3.428</td><td align="center" rowspan="1" colspan="1">109 </td></tr><tr><td align="left" rowspan="1" colspan="1">58 </td><td align="center" rowspan="1" colspan="1">1817</td><td align="center" rowspan="1" colspan="1">3.259</td><td align="center" rowspan="1" colspan="1">161 </td></tr><tr><td align="left" rowspan="1" colspan="1">60 </td><td align="center" rowspan="1" colspan="1">6042</td><td align="center" rowspan="1" colspan="1">3.781</td><td align="center" rowspan="1" colspan="1">48 </td></tr><tr><td align="left" rowspan="1" colspan="1">71 </td><td align="center" rowspan="1" colspan="1">256.8</td><td align="center" rowspan="1" colspan="1">2.41</td><td align="center" rowspan="1" colspan="1">1139 </td></tr><tr><td align="left" rowspan="1" colspan="1">77 </td><td align="center" rowspan="1" colspan="1">749.5</td><td align="center" rowspan="1" colspan="1">2.875</td><td align="center" rowspan="1" colspan="1">390 </td></tr><tr><td align="left" rowspan="1" colspan="1">78 </td><td align="center" rowspan="1" colspan="1">47.48</td><td align="center" rowspan="1" colspan="1">1.676</td><td align="center" rowspan="1" colspan="1">6160 </td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>124</bold></td><td align="center" rowspan="1" colspan="1"><bold><1</bold></td><td align="center" rowspan="1" colspan="1"><bold><0</bold></td><td align="center" rowspan="1" colspan="1"><bold>>292500</bold></td></tr><tr><td align="left" rowspan="1" colspan="1">130 </td><td align="center" rowspan="1" colspan="1">133.9</td><td align="center" rowspan="1" colspan="1">2.127</td><td align="center" rowspan="1" colspan="1">2184 </td></tr><tr><td align="left" rowspan="1" colspan="1">143 </td><td align="center" rowspan="1" colspan="1">179100</td><td align="center" rowspan="1" colspan="1">5.253</td><td align="center" rowspan="1" colspan="1">2 </td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>198 </bold></td><td align="center" rowspan="1" colspan="1"><bold><1</bold></td><td align="center" rowspan="1" colspan="1"><bold><0</bold></td><td align="center" rowspan="1" colspan="1"><bold>>292500</bold></td></tr><tr><td align="left" rowspan="1" colspan="1">208 </td><td align="center" rowspan="1" colspan="1">2563</td><td align="center" rowspan="1" colspan="1">3.409</td><td align="center" rowspan="1" colspan="1">114 </td></tr><tr><td align="left" rowspan="1" colspan="1">223 </td><td align="center" rowspan="1" colspan="1">58240</td><td align="center" rowspan="1" colspan="1">4.765</td><td align="center" rowspan="1" colspan="1">5 </td></tr><tr><td align="left" rowspan="1" colspan="1">232 </td><td align="center" rowspan="1" colspan="1">2212</td><td align="center" rowspan="1" colspan="1">3.345</td><td align="center" rowspan="1" colspan="1">132 </td></tr><tr><td align="left" rowspan="1" colspan="1">274 </td><td align="center" rowspan="1" colspan="1">344.2</td><td align="center" rowspan="1" colspan="1">2.537</td><td align="center" rowspan="1" colspan="1">850 </td></tr><tr><td align="left" rowspan="1" colspan="1">297 </td><td align="center" rowspan="1" colspan="1">431900</td><td align="center" rowspan="1" colspan="1">5.635</td><td align="center" rowspan="1" colspan="1">1 </td></tr><tr><td align="left" rowspan="1" colspan="1">324 </td><td align="center" rowspan="1" colspan="1">3582</td><td align="center" rowspan="1" colspan="1">3.554</td><td align="center" rowspan="1" colspan="1">82 </td></tr><tr><td align="left" rowspan="1" colspan="1">325 </td><td align="center" rowspan="1" colspan="1">734200</td><td align="center" rowspan="1" colspan="1">5.866</td><td align="center" rowspan="1" colspan="1">No inhibition </td></tr><tr><td align="left" rowspan="1" colspan="1">326</td><td align="center" rowspan="1" colspan="1">165600</td><td align="center" rowspan="1" colspan="1">5.219</td><td align="center" rowspan="1" colspan="1">2 </td></tr><tr><td align="left" rowspan="1" colspan="1">Positive control (No treatment)</td><td align="center" rowspan="1" colspan="1">292500</td><td align="center" rowspan="1" colspan="1">5.466</td><td align="center" rowspan="1" colspan="1"></td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list><country><li>Corée du Sud</li></country></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Cho, Won Kyung" sort="Cho, Won Kyung" uniqKey="Cho W" first="Won-Kyung" last="Cho">Won-Kyung Cho</name></noRegion><name sortKey="Choi, Yu Jeong" sort="Choi, Yu Jeong" uniqKey="Choi Y" first="Yu Jeong" last="Choi">Yu Jeong Choi</name><name sortKey="Kim, Hyunil" sort="Kim, Hyunil" uniqKey="Kim H" first="Hyunil" last="Kim">Hyunil Kim</name><name sortKey="Ma, Jin Yeul" sort="Ma, Jin Yeul" uniqKey="Ma J" first="Jin Yeul" last="Ma">Jin Yeul Ma</name><name sortKey="Yang, Hye Jin" sort="Yang, Hye Jin" uniqKey="Yang H" first="Hye Jin" last="Yang">Hye Jin Yang</name><name sortKey="Yim, Nam Hui" sort="Yim, Nam Hui" uniqKey="Yim N" first="Nam-Hui" last="Yim">Nam-Hui Yim</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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