1. Academic Validation
  2. Anti-viral effect of a compound isolated from Liriope platyphylla against hepatitis B virus in vitro

Anti-viral effect of a compound isolated from Liriope platyphylla against hepatitis B virus in vitro

  • Virus Res. 2014 Nov 4;192:16-24. doi: 10.1016/j.virusres.2014.07.015.
Tsurng-Juhn Huang 1 Yu-Chi Tsai 2 Shang-Yu Chiang 2 Guei-Jane Wang 3 Yu-Cheng Kuo 4 Yi-Chih Chang 5 Yi-Ying Wu 5 Yang-Chang Wu 6
Affiliations

Affiliations

  • 1 School of Medicine and Research Center for Biodiversity, China Medical University, Taichung 404, Taiwan. Electronic address: [email protected].
  • 2 Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • 3 Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan.
  • 4 Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 404, Taiwan.
  • 5 Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan.
  • 6 Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan; School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan; Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan. Electronic address: [email protected].
Abstract

The compound LPRP-Et-97543 was isolated from Liriope platyphylla roots and was observed to have potential anti-viral effects in HepG2.2.15 cells against hepatitis B virus (HBV). The Antiviral mode was further clarified, and the HBV-transfected Huh7 cells were used as the platform. During viral gene expression, LPRP-Et-97543 treatment had apparent effects on the viral precore/pregenomic and S/preS RNA. Promoter activity analysis demonstrated that LPRP-Et-97543 significantly reduced Core, S, and preS but not X promoter activities. Further examination showed that putative signaling pathways were involved in this inhibitory effect, indicating that NF-κB may serve a putative mediator of HBV gene regulation with LPRP-Et-97543. In addition, the nuclear expression of p65/p50 NF-κB member proteins was attenuated with LPRP-Et-97543 and augmented cytoplasmic IκBα protein levels but without affecting the expression of these proteins in HBV non-transfected cells during treatment. Moreover, LPRP-Et-97543 reduced the binding activity of NF-κB protein to CS1 element of HBV surface gene in a gel retardation analysis and inhibited CS1 containing promoter activity in HBV expressed cells. However, HBV transfection significantly enhances CS1 containing promoter activity without compound treatment in cells. Finally, transfection of the p65 expression plasmid significantly reversed the inhibitory effect of LPRP-Et-97543 on the replicated HBV DNA level in HBV positive cells. In conclusion, this study suggests that the mechanism of HBV inhibition by LPRP-Et-97543 may involve the feedback regulation of viral gene expression and viral DNA replication by HBV Viral Proteins, which interferes with the NF-κB signaling pathway.

Keywords

HepG2.2.15; Hepatitis B virus; Huh7; Liriope platyphylla; NF-κB.

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