Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis.

Abstract

OBJECTIVE:

Saikosaponin c (SSc), a compound purified from the traditional Chinese herb of Radix Bupleuri was previously identified to exhibit anti-HBV replication activity. However, the mechanism through which SSc acts against HBV remains unknown. In this study, we investigated the mechanism of SSc mediated anti-HBV activity.

METHODS:

HepG2.2.15 cells were cultured at 37 ℃ in the presence of 1-40 μg/mL of SSc or DMSO as a control. The expression profile of HBV markers, cytokines, HNF1α and HNF4α were investigated by real-time quantitative PCR, Elisa, Western blot and Dot blotting. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells was mediated by two small siRNAs specifically targeting HNF1α or HNF4α.

RESULTS:

We found that SSc stimulates IL-6 expression, leading to attenuated HNF1α and HNF4α expression, which further mediates suppression of HBV pgRNA synthesis. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells by RNA interference abrogates SSc's anti-HBV role. Moreover, SSc is effective to both wild-type and drug-resistant HBV mutants.

CONCLUSION:

SSc inhibits pgRNA synthesis by targeting HNF1α and HNF4α. These results indicate that SSc acts as a promising compound for modulating pgRNA transcription in the therapeutic strategies against HBV infection.

• Authors: Yanchao Pan, Zhiyi Ke, Hong Ye, Lina Sun, Xiaoyan Ding, Yun Shen, Runze Zhang, Jing Yuan
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 68 Issue 12 Pg. 1025-1034 (Dec 2019) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 31531682 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• HNF1A protein, human
• HNF4A protein, human
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens
• Hepatocyte Nuclear Factor 1-alpha
• Hepatocyte Nuclear Factor 4
• RNA, Small Interfering
• RNA, Viral
• Saponins
• pgRNA
• RNA
• Oleanolic Acid
• saikosaponin D

Topics

• Antiviral Agents (pharmacology)
• Hep G2 Cells
• Hepatitis B Surface Antigens (metabolism)
• Hepatitis B e Antigens (metabolism)
• Hepatitis B virus (drug effects, genetics, immunology, metabolism)
• Hepatocyte Nuclear Factor 1-alpha (genetics, metabolism)
• Hepatocyte Nuclear Factor 4 (genetics, metabolism)
• Humans
• Oleanolic Acid (analogs & derivatives, pharmacology)
• RNA (biosynthesis)
• RNA Interference
• RNA, Small Interfering (genetics)
• RNA, Viral (biosynthesis)
• Saponins (pharmacology)