title: Amelioration of influenza virus-induced reactive oxygen species formation by epigallocatechin gallate derived from green tea.
abstract: OBJECTIVE
  To study whether epigallocatechin gallate (EGCG), a green tea-derived polyphenol, exerted anti-influenza A virus activity in vitro and in vivo.
  
  
  METHODS
  Madin-Darby canine kidney (MDCK) cells were tested. The antiviral activity of EGCG in the cells was determined using hemagglutination assay and qPCR. Time of addition assay was performed to determine the kinetics of inhibition of influenza A by EGCG. The level of reactive oxygen species (ROS) were determined with confocal microscopy and flow cytometry. BALB/c mice were treated with EGCG (10, 20 or 40 mg·kg(-1)·d(-1), po) for 5 d. On the 3rd d of the treatment, the mice were infected with influenza A virus. Histopathological changes, lung index and virus titers in the lungs were determined.
  
  
  RESULTS
  Treatment of influenza A-infected MDCK cells with EGCG (1.25-100 nmol/L) inhibited influenza A replication in a concentration-dependent manner (the ED(50) value was 8.71±1.11 nmol/L). Treatment with EGCG (20 nmol/L) significantly suppressed the increased ROS level in MDCK cells following influenza A infection. In BALB/c mice infected with influenza virus, oral administration of EGCG (40 mg·kg(-1)·d(-1)) dramatically improved the survival rate, decreased the mean virus yields and mitigated viral pneumonia in the lungs, which was equivalent to oral administration of oseltamivir (40 mg·kg(-1)·d(-1)), a positive control drug.
  
  
  CONCLUSIONS
  The results provide a molecular basis for development of EGCG as a novel and safe chemopreventive agent for influenza A infection.
authors.affiliation: State Key Laboratory of Virology/Institute of Medical Virology/Research Center of Food and Drug Evaluation/State Laboratory of Antiviral and Tumor of Traditional Chinese Medicine, School of Medicine, Wuhan University, Wuhan 430071, China.
authors.forename: Jia-xin
authors.initials: JX
authors.lastname: Ling
authors.forename: Fei
authors.initials: F
authors.lastname: Wei
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jin-lin
authors.initials: JL
authors.lastname: Li
authors.forename: Liang-jun
authors.initials: LJ
authors.lastname: Chen
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Liu
authors.forename: Fan
authors.initials: F
authors.lastname: Luo
authors.forename: Hai-rong
authors.initials: HR
authors.lastname: Xiong
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: Zhan-qiu
authors.initials: ZQ
authors.lastname: Yang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000821:virology; D006168:Guinea Pigs; D006386:Hemagglutination Tests; D006387:Hemagglutination, Viral / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000254:growth & development; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011024:Pneumonia, Viral / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000821:virology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000998:Antiviral Agents; D017382:Reactive Oxygen Species; D002392:Catechin; C045651:epigallocatechin gallate