title: Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of Neutrophil Activation.
abstract: Andrographolide sulfonate treatment has been shown to improve clinical severe hand, foot, and mouth disease (HFMD) efficacies when combined with conventional therapy. 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 days 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 in vitro. We observed that MPO and S100A8/A9 levels were markedly elevated in the HFMD patients before clinical treatment. At 5 days post-medication, the MPO, S100A8/A9, histone, and interleukin-6 levels were markedly lower in the combination therapy group compared with the conventional therapy group. In vitro studies showed that andrographolide sulfonate inhibited lipopolysaccharide-stimulated 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 © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Research Center for Medical Sciences, Beijing Chao-Yang Hospital affiliated with Capital Medical University, Beijing, 100020, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wen
authors.affiliation: Department of Integrated TCM and Western Medicine, Beijing Youan Hospital affiliated with Capital Medical University, Beijing, 100069, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, Beijing Youan Hospital affiliated with Capital Medical University, Beijing, 100069, China.
authors.forename: Lianchun
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Emergency, Beijing Youan Hospital affiliated with Capital Medical University, Beijing, 100069, China.
authors.forename: Junhong
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science, Beijing, 100700, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Ding
authors.affiliation: Jiangxi Qingfeng Pharmaceutical Inc., Ganzhou, 341000, Jiangxi Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Integrated TCM and Western Medicine, Beijing Youan Hospital affiliated with Capital Medical University, Beijing, 100069, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science, Beijing, 100700, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Lv
authors.affiliation: Department of Integrated TCM and Western Medicine, Beijing Youan Hospital affiliated with Capital Medical University, Beijing, 100069, China.
authors.forename: Xiuhui
authors.initials: X
authors.lastname: Li
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D004224:Diterpenes / Q000627:therapeutic use*; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000188:drug therapy*; D006657:Histones / Q000097:blood; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D018375:Neutrophil Activation; D009195:Peroxidase / Q000097:blood; D017382:Reactive Oxygen Species / Q000378:metabolism; D009418:S100 Proteins / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004224:Diterpenes; D006657:Histones; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D009418:S100 Proteins; C030419:andrographolide; D009195:Peroxidase
keywords: andrographolide sulfonate; hand, foot, and mouth disease (HFMD); inflammation; neutrophil activation