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.

Determining novel candidate anti-hepatocellular carcinoma drugs using interaction networks and molecular docking between drug targets and natural compounds of SiNiSan

“…Recent experiments have shown that SNS is a remarkably effective treatment for hepatitis and liver injury ( Shu et al, 2018 ). The individual herbs that make up SNS have anti-inflammatory, anti-bacterial, anti-oxidation, anti-tumor, anti-proliferation, anti-angiogenic, anti-HBV, and apoptotic effects in vitro and in vivo ( Zhao et al, 2018 ; Li et al, 2020a ; Li et al, 2020b ; Ma et al, 2014a ; Ma et al, 2014b ; Sun et al, 2019 ; Xiang et al, 2019 ; Pan et al, 2019 ; Zhou et al, 2019 ; Lefaki et al, 2020 ).…”

“…Recent experiments have shown that SNS is a remarkably effective treatment for hepatitis and liver injury (Shu et al, 2018). The individual herbs that make up SNS have anti-inflammatory, anti-bacterial, anti-oxidation, anti-tumor, anti-proliferation, anti-angiogenic, anti-HBV, and apoptotic effects in vitro and in vivo (Zhao et al, 2018;Li et al, 2020a;Li et al, 2020b;Ma et al, 2014a;Ma et al, 2014b;Sun et al, 2019;Xiang et al, 2019;Pan et al, 2019;Zhou et al, 2019;Lefaki et al, 2020). In our research, there are 64 overlaps between drug targets and disease targets which are the important targets involved in the therapeutic mechanism of SNS, we studied 113 compounds and 64 target genes using the screening criteria and found that each bioactive compound acts on at least 1 HCC differential gene, core targets genes were PTGS2, ESR1, AR , NOS2, CCNA2 and CHEK1.…”

Peer Review #2 of "Determining novel candidate anti-hepatocellular carcinoma drugs using interaction networks and molecular docking between drug targets and natural compounds of SiNiSan (v0.1)"

“…Recent experiments have shown that SNS is a remarkably effective treatment for hepatitis and liver injury (Shu et al, 2018). The individual herbs that make up SNS have anti-inflammatory, antibacterial, anti-oxidation, anti-tumor, anti-proliferation, anti-angiogenic, anti-HBV, and apoptotic effects in vitro and in vivo (Zhao et al, 2018;Sun et al, 2019;Xiang et al, 2019;Pan et al, 2019); Zhou et al, 2019;Lefaki et al, 2020). 2020:04:48251:2:1:NEW 28 Nov 2020) Manuscript to be reviewed In our research, there are 64 overlaps between drug targets and disease targets which are the important targets involved in the therapeutic mechanism of SNS, we studied 113 compounds and target genes using the screening criteria and found that each bioactive compound acts on at least HCC differential gene, core targets genes were PTGS2, ESR1, AR , NOS2, CCNA2 and CHEK1.…”

<p>Research Progress on Classical Traditional Chinese Medicine Jieyu Pills in the Treatment of Depression</p>

“…It is used to treat liver qi stagnation, chest and rib pain, anal prolapse, uterine prolapse, and irregular menstruation. In recent years, research on the application of RB has mainly focused on its use against depression, 24 for inhibiting cancer growth and metastasis, 25 anti-hepatitis B virus (HBV) effects, 26 antioxidative, anti-inflammatory, and hepatoprotective effects, 27 antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects, 28,29 antiepileptic effect, 30 and its use for treating AD. 31 Although there is an extensive range of clinical applications of RB, recent research has mainly focused on its antidepressant effect.…”