Synthesis and antiviral effects of isosteviol-derived analogues against the hepatitis B virus

Tsurng Juhn Huang, Bo Hon Chou, Cheng Wen Lin, Jen Hsien Weng, Chang Hung Chou, Li Ming Yang, Shwu Jiuan Lin

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Among several isosteviol-derived analogues, NC-8 (ent-16-oxobeyeran-19-N- methylureido) showed inhibitory potency against the hepatitis B virus (HBV) in HepG2 2.2.15 cells. Its anti-HBV mechanism was then next investigated in a human hepatoma cell culture system. Results showed that it specifically inhibited viral gene expression and reduced the level of encapsidated viral DNA intermediates in Huh7 cells that expressed replicating HBV. It also potently attenuated all viral promoter activity in HBV-expressing Huh7 cells, but not in cells lacking HBV expression. By examining its antiviral mechanism in cellular signaling pathways, NC-8 was found to inhibit the activity of the nuclear factor (NF)-κB element-containing promoter, but only slightly enhanced activities of activator protein (AP)-1- and interferon-sensitive response element (ISRE)-containing promoters in HBV-expressing cells. NC-8 also significantly eliminated NF-κB (p65/p50) and Toll-like receptor (TLR)2 proteins, but increased the IκBα protein level in a dose-dependent manner in HBV-transfected Huh7 cells, while these protein levels were apparently unchanged in non-transfected cells. Meanwhile, NC-8-treated nuclear extracts that co-expressed HBV inhibited the binding of NF-κB to the CS1 site of HBV major surface gene and specifically attenuated CS1-containing promoter activity. Taken together, this study suggests that the antiviral mechanism of NC-8 appears to be mediated by disturbing replication and gene expression of HBV and by inhibiting the host TLR2/NF-κB signaling pathway.

Original languageEnglish
Pages (from-to)107-114
Number of pages8
JournalPhytochemistry
Volume99
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Hepatitis B virus
  • Human hepatoma cells
  • Isosteviol derivative
  • NF-κB
  • TLR2

ASJC Scopus subject areas

  • Plant Science
  • Biochemistry
  • Molecular Biology
  • Horticulture
  • Medicine(all)

Fingerprint Dive into the research topics of 'Synthesis and antiviral effects of isosteviol-derived analogues against the hepatitis B virus'. Together they form a unique fingerprint.

  • Cite this