title: In vivo and in vitro antiviral effects of berberine on influenza virus.
abstract: OBJECTIVE
  To explore the potential effects of berberine on influenza virus infection both in vitro and in vivo.
  
  
  METHODS
  In vitro anti-influenza virus assays were performed by cytopathogenic effect and neuraminidase assays in Madin Darby canine kidney cells. In vivo anti-influenza virus assays were performed on the viral pneumonia model of mice. The numbers of mice that died within day 2 to day 14 postinfection were recorded to calculate the mortality. On days 2, 4, and 6, the viral titers in the lungs were determined by hemagglutination assay; hematoxylin/eosin staining was used to assess the pathogenic changes of lung tissues; the concentrations of tumor necrosis factor-alpha (TNF-α) and monocyte specific chemoattractant molecule (MCP-1) were measured by radio immunoassay or enzyme-linked immunosorbent assay; the concentrations of nitric oxide (NO) and inducible nitric oxide synthetase (iNOS) were detected by colorimetric method; reverse transcription polymerase chain reaction was used to detect the mRNA level of TNF-α and MCP-1.
  
  
  RESULTS
  Berberine showed inhibitory effects on cytopathogenic effects and neuraminidase activity of virus, with the therapeutic index 9.69. In vivo, berberine decreased mice mortality from 90% to 55%, reduced virus titers in the lungs on day 2 postinfection (P<0.05). The lung histology scores were 1.50 ± 0.67, 4.50 ± 1.00, and 5.50 ± 1.00 in the berberine group on days 2, 4, and 6, respectively, which were significantly reduced compared to 2.17 ± 0.22, 6.83 ± 0.44, and 8.50 ± 0.33 in the infected group (P<0.05). The productions of NO and iNOS were repressed by berberine compared with those in the infected group (P<0.01). The transcription and expression of TNF-α were inhibited by berberine on day 4 (P<0.01) and day 6 (P<0.05), and those of MCP-1 were inhibited on day 6 (P<0.01) compared with the infected group.
  
  
  CONCLUSIONS
  Berberine exhibited antiviral effects on the influenza virus both in vitro and in vivo. The possible therapeutic mechanism of berberine on influenza-induced viral pneumonia might be inhibiting the virus infection, as well as improving the pathogenic changes by repressing inflammatory substances release.
authors.affiliation: Key Laboratory of Chinese Medicine on Viral Diseases, Ministry of Education, Microbiology and Immunology Department, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Ji-qian
authors.initials: JQ
authors.lastname: Li
authors.forename: Ye-ji
authors.initials: YJ
authors.lastname: Kim
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Hao
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D005260:Female; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D009439:Neuraminidase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000201:enzymology; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016019:Survival Analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D018932:Chemokine CCL2; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D009439:Neuraminidase