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However, the mechanisms for its therapeutic effects remain elusive. In this study, we aimed to investigate whether andrographolide sulfonate exerts its efficacy by acting on neutrophil activation. We obtained serial plasma samples at two time points (before and after 5\u2009days of therapy) from 28 HFMD patients who received conventional therapy and 18 patients who received combination therapy (andrographolide sulfonate plus conventional therapy). Then, we measured plasma myeloperoxidase (MPO), S100A8\/A9, histone, and inflammatory cytokine levels. Furthermore, we examined if andrographolide sulfonate had direct effects on neutrophil activation <jats:italic>in vitro<\/jats:italic>. We observed that MPO and S100A8\/A9 levels were markedly elevated in the HFMD patients before clinical treatment. At 5\u2009days post\u2010medication, the MPO, S100A8\/A9, histone, and interleukin\u20106 levels were markedly lower in the combination therapy group compared with the conventional therapy group. <jats:italic>In vitro<\/jats:italic> studies showed that andrographolide sulfonate inhibited lipopolysaccharide\u2010stimulated neutrophil activation, demonstrated by the decreased production of reactive oxygen species and cytokines. These data indicate that neutrophil activation modulation by andrographolide sulfonate may be a critical determinant for its clinical HFMD treatment efficacy. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/ptr.5361","type":"journal-article","created":{"date-parts":[[2015,5,9]],"date-time":"2015-05-09T08:10:14Z","timestamp":1431159014000},"page":"1161-1167","source":"Crossref","is-referenced-by-count":21,"title":["Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of Neutrophil Activation"],"prefix":"10.1002","volume":"29","author":[{"given":"Tao","family":"Wen","sequence":"first","affiliation":[{"name":"Research Center for Medical Sciences Beijing Chao\u2010Yang Hospital affiliated with Capital Medical University  Beijing 100020 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Integrated TCM and Western Medicine Beijing Youan Hospital affiliated with Capital Medical University  Beijing 100069 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianchun","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Beijing Youan Hospital affiliated with Capital Medical University  Beijing 100069 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Beijing Youan Hospital affiliated with Capital Medical University  Beijing 100069 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaorong","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Science  Beijing 100700 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangxi Qingfeng Pharmaceutical Inc.  Ganzhou 341000 Jiangxi Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Integrated TCM and Western Medicine Beijing Youan Hospital affiliated with Capital Medical University  Beijing 100069 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiping","family":"Lv","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Science  Beijing 100700 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuhui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Integrated TCM and Western Medicine Beijing Youan Hospital affiliated with Capital Medical University  Beijing 100069 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,5,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1148-z"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eujim.2011.11.004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.32.1385"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","unstructured":"ChenYY HsiehCY JayakumarT et al.2014.Andrographolide induces vascular smooth muscle cell apoptosis through a SHP\u20101\u2010PP2A\u2010p38MAPK\u2010p53 cascade. 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