Downregulation of cellular c-Jun N-terminal protein kinase and NF-κB activation by berberine may result in inhibition of herpes simplex virus replication

Antimicrob Agents Chemother. 2014 Sep;58(9):5068-78. doi: 10.1128/AAC.02427-14. Epub 2014 Jun 9.


Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. Some reports show that berberine exhibits anti-inflammatory, antitumor, and antiviral properties by modulating multiple cellular signaling pathways, including p53, nuclear factor κB (NF-κB), and mitogen-activated protein kinase. In the present study, we investigated the antiviral effect of berberine against herpes simplex virus (HSV) infection. Current antiherpes medicines such as acyclovir can lessen the recurring activation when used early at infection but are unable to prevent or cure infections where treatment has selected for resistant mutants. In searching for new antiviral agents against herpesvirus infection, we found that berberine reduced viral RNA transcription, protein synthesis, and virus titers in a dose-dependent manner. To elucidate the mechanism of its antiviral activity, the effect of berberine on the individual steps of viral replication cycle of HSV was investigated via time-of-drug addition assay. We found that berberine acted at the early stage of HSV replication cycle, between viral attachment/entry and genomic DNA replication, probably at the immediate-early gene expression stage. We further demonstrated that berberine significantly reduced HSV-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. Moreover, we found that berberine also depressed HSV-induced c-Jun N-terminal kinase (JNK) phosphorylation but had little effect on p38 phosphorylation. Our results suggest that the berberine inhibition of HSV infection may be mediated through modulating cellular JNK and NF-κB pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Berberine / pharmacology*
  • Cell Line
  • DNA Replication / drug effects*
  • DNA Replication / genetics
  • Down-Regulation / drug effects*
  • Down-Regulation / genetics
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • HEK293 Cells
  • Humans
  • I-kappa B Proteins / genetics
  • JNK Mitogen-Activated Protein Kinases / genetics*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / genetics*
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Simplexvirus / drug effects*
  • Simplexvirus / genetics
  • Virus Replication / drug effects*
  • Virus Replication / genetics


  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Berberine
  • NF-KappaB Inhibitor alpha
  • JNK Mitogen-Activated Protein Kinases