Phyllanthus amarus down-regulates hepatitis B virus mRNA transcription and replication.
The Phyllanthus amarus plant shows potential for treating hepatitis B virus. To define the mechanism of action of P. amarus, we used HepG2 2.2.15 cells, which support hepatitis B virus replication. P. amarus inhibited hepatitis B virus polymerase activity, decreased episomal hepatitis B virus DNA content and suppressed virus release into culture medium. To examine transcriptional control mechanisms, we used G26 hepatitis B virus transgenic mice, which produce serum HBsAg but neither HBcAg nor virion particles. When P. amarus was administered to transgenic mice, hepatic HBsAg mRNA levels decreased, indicating transcriptional or post-transcriptional down-regulation of the transgene. Increase in hepatitis B virus mRNA expression after stimulation of the glucocorticoid responsive element was also suppressed by P. amarus, suggesting involvement of the hepatitis B virus enhancer in this response. Disruption by P. amarus of hepatitis B virus polymerase activity, mRNA transcription and replication supports its role as an antiviral agent.
Lee
C D
CD
Marion Bessin Liver Research Center, Madras, India.
Ott
M
M
Thyagarajan
S P
SP
Shafritz
D A
DA
Burk
R D
RD
Gupta
S
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D019384:Nucleic Acid Synthesis Inhibitors; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D010936:Plant Extracts; D012333:RNA, Messenger