title: Evaluation of the anti-neuraminidase activity of the traditional Chinese medicines and determination of the anti-influenza A virus effects of the neuraminidase inhibitory TCMs in vitro and in vivo.
abstract: ETNOPHARMACOLOGICAL RELEVANCE: Neuraminidase (NA) inhibitors are currently the most effective drugs to treat influenza A viruses infection. Many traditional Chinese medicines (TCMs) have been used in the clinics to treat influenza. The anti-viral mechanisms of these TCMs and their inhibitory effects towards NA need to be systematically tested.
  
  
  OBJECTIVE
  To evaluate the anti-NA activity of the TCMs and the anti-influenza A virus effects of the NA inhibitory TCMs in vitro and in vivo.
  
  
  METHODS
  We tested the inhibitory activity of water extracts from 439 TCMs towards NA. The in vitro anti-influenza virus activities of the 5 TCMs were evaluated using the strain A/California/7/2009 (H1N1) NYMC X-179A of influenza A virus. A randomly selected TCM with NA inhibitory activity, Melia toosendan extract, was further evaluated using a mouse model infected with influenza A virus.
  
  
  RESULTS
  Five TCMs, Duchesnea indica (Andr.) Focke [Fragaria indica Andr.], Liquidambar formosana Hance., Lithospermum erythrorhizon Sieb. et Zucc., Melia toosendan Sieb. et Zucc., and Prunella vulgaris L., exerted potent inhibitory activity towards NA. These TCMs in the range of 25-250 μg/mL had the ability to reduce virus-induced cytopathic effect (CPE) and the virus yield in MDCK cells. Melia toosendan significantly reduced death rate and prolonged mean day to death (MDD) of the viral infected mice.
  
  
  CONCLUSIONS
  This study describes five TCMs exerted strong inhibitory activities towards NA, and exhibited antiviral effect against influenza A virus by reducing viral reproduction and reduced CPE of the viral infected cells. Melia toosendan, significantly reduced death rate and prolonged survival of the H1N1 viral infected mice.
authors.affiliation: Key Laboratory of Molecular Enzymology and Enzyme Engineering of Ministry Education, Jilin University, Changchun 130012, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jingwei
authors.initials: J
authors.lastname: Xu
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.forename: Fengchun
authors.initials: F
authors.lastname: Qi
authors.forename: Minli
authors.initials: M
authors.lastname: Fang
authors.forename: Dahai
authors.initials: D
authors.lastname: Yu
authors.forename: Xuexun
authors.initials: X
authors.lastname: Fang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000201:enzymology; D008516:Medicine, Chinese Traditional; D051379:Mice; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology; D012997:Solvents / Q000737:chemistry; D013997:Time Factors; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D012997:Solvents; D014764:Viral Proteins; D014867:Water; D009439:Neuraminidase