title: Downregulation of cellular c-Jun N-terminal protein kinase and NF-κB activation by berberine may result in inhibition of herpes simplex virus replication.
abstract: 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.
authors.affiliation: Center for Public Health Research, School of Medicine, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Siwei
authors.initials: S
authors.lastname: Song
authors.affiliation: Center for Public Health Research, School of Medicine, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Center for Public Health Research, School of Medicine, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Center for Public Health Research, School of Medicine, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Deyan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Center for Public Health Research, School of Medicine, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Public Health Research, School of Medicine, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Airong
authors.initials: A
authors.lastname: Su
authors.affiliation: Center for Public Health Research, School of Medicine, Nanjing University, Nanjing, People's Republic of China State Key Lab of Analytical Chemistry for Life Science, Nanjing University, Nanjing, People's Republic of China wzhw@nju.edu.cn.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wu
mesh_terms: D001599:Berberine / Q000494:pharmacology*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D018139:Simplexvirus / Q000187:drug effects* / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D001599:Berberine; D000072000:NF-KappaB Inhibitor alpha; D048031:JNK Mitogen-Activated Protein Kinases