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.

AIMS:

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: Keng-Hsin Lan, Ying-Wen Wang, Wei-Ping Lee, Keng-Li Lan, Szu-Han Tseng, Li-Rong Hung, Sang-Hue Yen, Han-Chieh Lin, Shou-Dong Lee
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 32 Issue 6 Pg. 989-97 (Jul 2012) ISSN: 1478-3231 [Electronic] United States
• PMID: 22098176 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Antiviral Agents
• Biphenyl Compounds
• Drugs, Chinese Herbal
• Interferon-alpha
• Lignans
• Viral Proteins
• honokiol

Topics

• Antiviral Agents (pharmacology)
• Biphenyl Compounds (pharmacology)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Drugs, Chinese Herbal (pharmacology)
• Gene Expression Regulation, Viral (drug effects)
• Genes, Reporter
• Genotype
• HEK293 Cells
• Hepacivirus (drug effects, genetics, growth & development, metabolism)
• Humans
• Interferon-alpha (pharmacology)
• Lignans (pharmacology)
• Magnolia
• Phenotype
• Plants, Medicinal
• Protein Biosynthesis (drug effects)
• Transfection
• Viral Proteins (biosynthesis, genetics)
• Virus Internalization (drug effects)
• Virus Replication (drug effects)