Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV enhancer I and cellular transcription factors

M. Ott, S. P. Thyagarajan, Sanjeev Gupta

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

The Phyllanthus amarus plant suppresses HBV mRNA transcription in vitro and exhibits therapeutic potential in chronic HBV carriers, although further work is necessary to define its mechanism of action. Analysis in HuH-7 cells with transfected plasmids using a luciferase reporter showed that P. amarus specifically inhibited HBV enhancer I activity. To identify the mechanism of this HBV enhancer I inhibition, liver-enriched cellular transcription factors were co-expressed in HuH-7 cells. The C/EBPα and β, as well as HNF-3α and β transcription factors, significantly up-regulated the HBV enhancer I activity. In contrast, co-transfection of HNF-1α or β had no effect upon the HBV enhancer I activity. Exposure to P. amarus inhibited C/EBPα- and β-mediated up-regulation of HBV enhancer I activity in a dose-dependent manner, whereas HNF-3α- and β-mediated up-regulation of HBV enhancer I: was unaffected. In vitro gel shifts showed that P. amarus inhibited complexing of C/EBP transcription factors to a consensus oligonucleotide sequence, whereas DNA binding of AP-1 and SP-1 transcription factors was unaffected. As P. amarus down-regulates HBV mRNA transcription by a specific mechanism involving interactions between HBV enhancer I and C/EBP transcription factors, purification and further analysis of the active P. amarus component will advance insights into its antiviral activity.

Original languageEnglish (US)
Pages (from-to)908-915
Number of pages8
JournalEuropean Journal of Clinical Investigation
Volume27
Issue number11
StatePublished - 1997

Fingerprint

Phyllanthus
Viruses
Hepatitis B virus
Transcription Factors
Transcription
Transcription Factor 3
Messenger RNA
DNA sequences
Transcription Factor AP-1
Up-Regulation
Luciferases
Oligonucleotides
Liver
Purification
Antiviral Agents
Plasmids
Gels
Consensus Sequence
Transfection
Down-Regulation

Keywords

  • Hepatitis B virus
  • Liver
  • Medicinal plant
  • Treatment

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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AU - Thyagarajan, S. P.

AU - Gupta, Sanjeev

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