Antiviral Effect Of Berberine Against Herpes Simplex Virus

Berberine, a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids, is found in genus Berberis and is used as a traditional medicine or dietary supplement against fungal, bacterial and viral infections. Some reports showed that berberine exhibited anti-inflammatory, anti-tumor and antiviral properties by modulating multiple cellular signaling pathways, including p53, nuclear factor kappaB (NF-κB) and mitogen-activated protein kinase (MAPK). In the current study, we investigated the antiviral effect of berberine against herpes simplex virus (HSV) infection. Current anti-herpes medicines such as acyclovir can lessen the recurring activation when used early at infection but are unable to prevent or cure infections and have encountered 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 the infection cycle of HSV was investigated in comparison to reference drugs. We found that berberine acted at the early stage of HSV life cycle, between viral attachment/entry and genomic DNA replication, probably at the immediate early (IE) gene expression. We further demonstrated that berberine significantly reduced HSV-induced NF-κB activation, as well as IκB-α degradation and p65 translocation. Moreover, we found that berberine also depressed HSV-induced c-Jun N-terminal kinases (JNK) phosphorylation, but had effect on p38 phosphorylation. Our results suggested that the inhibition of HSV infection might be mediated through modulating cellular NF-κB and JNK pathway.