title: Multiple effects of Honokiol on the life cycle of hepatitis C virus.
abstract: BACKGROUND
  Honokiol, a small active molecular compound extracted from magnolia, has recently been shown to inhibit hepatitis C virus (HCV) infection in vitro.
  
  
  OBJECTIVE
  This study further characterized aspects of the HCV lifecycle affected by the antiviral functions of honokiol.
  
  
  METHODS
  The influence of honokiol on HCV infection, entry, translation and replication was assessed in Huh-7.5.1 cells using cell culture-derived HCV (HCVcc), HCV pseudo-type (HCVpp) and sub-genomic replicons.
  
  
  RESULTS
  Honokiol had strong antiviral effect against HCVcc infection at non-toxic concentrations. Combined with interferon-α, its inhibitory effect on HCVcc was more profound than that of ribavirin. Honokiol inhibited the cell entry of lentiviral particles pseudo-typed with glycoproteins from HCV genotypes 1a, 1b, and 2a, but not of the vesicular stomatitis virus. It had inefficient activity on HCV internal ribosome entry site (IRES)-translation at concentrations with significant anti-HCVcc effects. The expression levels of components of replication complex, NS3, NS5A and NS5B, were down-regulated by honokiol in a dose-dependent manner. It also inhibited HCV replication dose dependently in both genotypes 1b and 2a sub-genomic replicons.
  
  
  CONCLUSIONS
  Honokiol inhibits HCV infection by targeting cell entry and replication and, only at a concentration >30 μM, IRES-mediated translation of HCV life cycle. Based on its high therapeutic index (LD(50) /EC(90)  = 5.4), honokiol may be a promising drug for the treatment of HCV infection.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Keng-Hsin
authors.initials: KH
authors.lastname: Lan
authors.forename: Ying-Wen
authors.initials: YW
authors.lastname: Wang
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Lee
authors.forename: Keng-Li
authors.initials: KL
authors.lastname: Lan
authors.forename: Szu-Han
authors.initials: SH
authors.lastname: Tseng
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Hung
authors.forename: Sang-Hue
authors.initials: SH
authors.lastname: Yen
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D017930:Genes, Reporter; D005838:Genotype; D057809:HEK293 Cells; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology*; D031566:Magnolia; D010641:Phenotype; D010946:Plants, Medicinal; D014176:Protein Biosynthesis / Q000187:drug effects; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000998:Antiviral Agents; D001713:Biphenyl Compounds; D004365:Drugs, Chinese Herbal; D016898:Interferon-alpha; D017705:Lignans; D014764:Viral Proteins; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols