Samarangenin B from Limonium sinense Suppresses Herpes Simplex Virus
Type 1 Replication in Vero Cells by Regulation of Viral Macromolecular
Synthesis
Yuh-Chi Kuo,1,2* Lie-Chwen Lin,1 Wei-Jern Tsai,1 Cheng-Jen Chou,1
Szu-Hao Kung,3 and Yen-Hui Ho1
National Research Institute of Chinese Medicine,1 Institute of Life
Science, Fu-Jen University,2 Department of Medical Technology and
Institute of Biotechnology in Medicine, National Yang-Ming University,
Taipei, Taiwan3

Received 30 November 2001/ Returned for modification 12 March 2002/
Accepted 30 May 2002

Inhibitory effects of ethanolic extracts from 10 Chinese herbs on
herpes simplex virus type 1 (HSV-1) replication were investigated. By a
bioassay-guided fractionation procedure, samarangenin B (Sam B) was
isolated from Limonium sinense; Sam B significantly suppressed HSV-1
multiplication in Vero cells without apparent cytotoxicity.
Time-of-addition experiments suggested that the inhibitory action of
Sam B on HSV-1 replication was not due to the blocking of virus
adsorption. In an attempt to further localize the point in the HSV-1
replication cycle where arrest occurred, a set of key regulatory events
leading to viral multiplication was examined, including viral
immediate-early (), early (ß), and late () gene expression and DNA
replication. Results indicated that levels of glycoprotein B (gB), gC,
gD, gG, and infected-cell protein 5 (ICP5) expression and gB mRNA
expression in Vero cells were impeded by Sam B. Data from PCR showed
that replication of HSV-1 DNA in Vero cells was arrested by Sam B.
Furthermore, Sam B decreased DNA polymerase, ICP0, and ICP4 gene
expression in Vero cells. Results of an electrophoretic mobility shift
assay demonstrated that Sam B interrupted the formation of an
-trans-induction factor/C1/Oct-1/GARAT multiprotein complex. The
mechanisms of antiviral action of Sam B seem to be mediated, at least
in part, by inhibiting HSV-1  gene expression, including expression of
the ICP0 and ICP4 genes, by blocking ß transcripts such as DNA
polymerase mRNA, and by arresting HSV-1 DNA synthesis and structural
protein expression in Vero cells. These results show that Sam B is an
antiviral agent against HSV-1 replication.

http://aac.asm.org/cgi/content/abstract/46/9/2854