title: Effects of flavonoid-induced oxidative stress on anti-H5N1 influenza a virus activity exerted by baicalein and biochanin A.
abstract: BACKGROUND
  Different flavonoids are known to interfere with influenza A virus replication. Recently, we showed that the structurally similar flavonoids baicalein and biochanin A inhibit highly pathogenic avian H5N1 influenza A virus replication by different mechanisms in A549 lung cells. Here, we investigated the effects of both compounds on H5N1-induced reactive oxygen species (ROS) formation and the role of ROS formation during H5N1 replication.
  
  
  RESULTS
  Baicalein and biochanin A enhanced H5N1-induced ROS formation in A549 cells and primary human monocyte-derived macrophages. Suppression of ROS formation induced by baicalein and biochanin A using the antioxidant N-acetyl-L-cysteine strongly increased the anti-H5N1 activity of both compounds in A549 cells but not in macrophages.
  
  
  CONCLUSIONS
  These findings emphasise that flavonoids induce complex pharmacological actions some of which may interfere with H5N1 replication while others may support H5N1 replication. A more detailed understanding of these actions and the underlying structure-activity relationships is needed to design agents with optimised anti-H5N1 activity.
authors: Martin
authors: M
authors: Michaelis
authors: Patchima
authors: P
authors: Sithisarn
authors: Institute for Medical Virology, Clinics of the Goethe-University, Paul Ehrlich-Str, 40, 60596 Frankfurt am Main, Germany. cinatl@em.uni-frankfurt.de.
authors: Jindrich
authors: J
authors: Cinatl
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000502:physiology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D000998:Antiviral Agents; D044950:Flavanones; D005419:Flavonoids; D017382:Reactive Oxygen Species; C006680:baicalein; D019833:Genistein; C004541:biochanin A; D000111:Acetylcysteine