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Saikosaponin C Exerts anti-HBV Effects by Attenuating HNF1α and HNF4α Expression to Suppress HBV pgRNA Synthesis

Saikosaponin C Exerts anti-HBV Effects by Attenuating HNF1α and HNF4α Expression to Suppress HBV pgRNA Synthesis

Yanchao Pan, Zhiyi Ke, Hong Ye, Lina Sun, Xiaoyan Ding, Yun Shen, Runze Zhang, Jing Yuan

Inflamm Res. 2019 Dec;68(12):1025-1034.

PMID: 31531682

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP20736087	Saikosaponin C		20736-08-7	Price

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