Antiviral effect of forsythoside A from Forsythia suspensa (Thunb.) Vahl fruit against influenza A virus through reduction of viral M1 protein

J Ethnopharmacol. 2017 Sep 14;209:236-247. doi: 10.1016/j.jep.2017.07.015. Epub 2017 Jul 14.

Abstract

Ethnopharmacological relevance: Yinqiaosan is a classical traditional Chinese medicine formula, which has been used to treat respiratory diseases since ancient China. It consists of nine herbs and among them, Forsythia suspensa (Thunb.) Vahl fruit is one of the major herbal components. Despite the long history of Yinqiaosan, the active compounds and the mechanisms of action of this formula remain elusive.

Aim of the study: The present study aimed to examine the suppressive effect of Yinqiaosan on influenza virus and to identify the active components in the formula targeting influenza.

Materials and methods: Anti-influenza virus effect of Yinqiaosan was assessed by tissue culture infective dose assay, and was also tested in an in vivo mouse model. Active compound from the formula was identified with a bioactivity-guided fractionation scheme. The potential mode of action of the compound was further investigated by identifying the host cell signaling pathways and viral protein production using in vitro cell culture models.

Results: Our results showed that forsythoside A from Forsythia suspensa (Thunb.) Vahl fruit, a major herbal component in Yinqiaosan, reduced the viral titers of different influenza virus subtypes in cell cultures and increased the survival rate of the mice in an in vivo influenza virus infection model. Further experiments on the mode of action of forsythoside A showed that it reduced the influenza M1 protein, which in turn intervened the budding process of the newly formed virions and eventually limited the virus spread.

Conclusion: Results of our present study provides scientific evidence to support to the application of a traditional herbal formula. We also identify novel candidate compound for future drug development against influenza virus.

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / therapeutic use
  • Cell Line
  • Dogs
  • Dose-Response Relationship, Drug
  • Forsythia / chemistry*
  • Fruit / chemistry*
  • Gene Expression Regulation, Viral / drug effects
  • Glycosides / administration & dosage
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • Influenza A virus / drug effects*
  • Mice
  • Orthomyxoviridae Infections / drug therapy
  • Orthomyxoviridae Infections / virology*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*
  • Virus Cultivation

Substances

  • Antiviral Agents
  • Glycosides
  • M1 protein, Influenza A virus
  • Viral Matrix Proteins
  • forsythiaside