title: Formononetin inhibits enterovirus 71 replication by regulating COX- 2/PGE₂ expression.
abstract: BACKGROUND
  The activation of ERK, p38 and JNK signal cascade in host cells has been demonstrated to up-regulate of enterovirus 71 (EV71)-induced cyclooxygenase-2 (COX-2)/ prostaglandins E2 (PGE₂) expression which is essential for viral replication. So, we want to know whether a compound can inhibit EV71 infection by suppressing COX-2/PGE₂ expression.
  
  
  METHODS
  The antiviral effect of formononetin was determined by cytopathic effect (CPE) assay and the time course assays. The influence of formononetin for EV71 replication was determined by immunofluorescence assay, western blotting assay and qRT-PCR assay. The mechanism of the antiviral activity of formononetin was determined by western blotting assay and ELISA assay.
  
  
  RESULTS
  Formononetin could reduce EV71 RNA and protein synthesis in a dose-dependent manner. The time course assays showed that formononetin displayed significant antiviral activity both before (24 or 12 h) and after (0-6 h) EV71 inoculation in SK-N-SH cells. Formononetin was also able to prevent EV71-induced cytopathic effect (CPE) and suppress the activation of ERK, p38 and JNK signal pathways. Furthermore, formononetin could suppress the EV71-induced COX-2/PGE₂ expression. Also, formononetin exhibited similar antiviral activities against other members of Picornaviridae including coxsackievirus B2 (CVB2), coxsackievirus B3 (CVB3) and coxsackievirus B6 (CVB6).
  
  
  CONCLUSIONS
  Formononetin could inhibit EV71-induced COX-2 expression and PGE₂ production via MAPKs pathway including ERK, p38 and JNK. Formononetin exhibited antiviral activities against some members of Picornaviridae. These findings suggest that formononetin could be a potential lead or supplement for the development of new anti-EV71 agents in the future.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. hq_wangimb@163.com.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. zhangdajun2008@126.com.
authors.forename: Dajun
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. gemiao0708@126.com.
authors.forename: Miao
authors.initials: M
authors.lastname: Ge
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. l-z-r@263.net.
authors.forename: Zhuorong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. jiang.jdong@163.com.|Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. jiang.jdong@163.com.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. yuhuanlibj@126.com.
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D029821:Enterovirus A, Human / Q000187:drug effects* / Q000502:physiology; D004769:Enterovirus Infections / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D007529:Isoflavones; D011458:Prostaglandins E; C007768:formononetin; D051546:Cyclooxygenase 2