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Inhibitory activities of Ranunculus japonicus Thunb. ethanol extract against hepatitis B virus
Minhui Luo1, Zhuohang Chen2, Miaoya Liu3
1School of Public Health, Southern Medical University, Guangzho, China.
Insights
This study reveals that Ranunculus japonicus Thunb. extract inhibits hepatitis B virus (HBV) replication by targeting capsid assembly and cccDNA formation, offering a potential new therapeutic avenue for chronic HBV infection.
Area of Science:
- Hepatology
- Virology
- Phytochemistry
Background:
- Chronic hepatitis B virus (HBV) infection is a global health challenge.
- Persistent viral cccDNA in hepatocytes prevents current cures.
- Medicinal herbs are screened for novel anti-HBV agents.
Purpose of the Study:
- To investigate the anti-HBV activity of Ranunculus japonicus Thunb. ethanol extract.
- To elucidate the mechanism of action of the extract on HBV replication.
Main Methods:
- Screening of medicinal herbs for anti-HBV effects.
- Analysis of HBV e antigen (HBeAg) production.
- Assessment of viral capsid assembly, pgRNA, and DNA levels.
- Evaluation of cccDNA formation efficiency.
Main Results:
- Ranunculus japonicus Thunb. extract reduced HBeAg production.
- The extract inhibited viral capsid assembly and delayed RC DNA formation.
- Significant reduction in cccDNA levels and formation efficiency was observed.
- HBV replication was inhibited at multiple stages.
Conclusions:
- Ranunculus japonicus Thunb. extract demonstrates multi-step inhibition of HBV replication.
- The extract shows significant potential in inhibiting capsid assembly and cccDNA formation.
- This herb extract may offer a novel therapeutic strategy against chronic HBV infection.
Abstract:
The chronic hepatitis B virus (HBV) infection is a worldwide public health problem, which cannot be cured by current therapeutics due to the persistence of viral CCC DNA in the infected hepatocytes. Screening from medicinal herbs for anti-HBV activities showed that the ethanol extract from Ranunculus japonicus Thunb. could decrease the production of HBV e antigen (HBeAg). Further study showed that the extract had no effect on core protein expression but significantly reduced the efficiency of viral capsid assembly. The levels of viral pgRNA and total core DNA were not affected significantly. However, the ratio of RC DNA/SS DNA decreased, indicating that the conversion of RC DNA from SS DNA was delayed by the extract. More interestingly, though similar levels of RC DNA were accumulated, the CCC DNA level and its formation efficiency were reduced significantly, which was also consistent with the decreased level of HBeAg, indicating that R. japonicus Thunb. extract could inhibit the CCC DNA formation. Together, this study found that R. japonicus Thunb. extract could inhibit HBV replication at multiple steps, especially showed significant inhibitory effects on capsid assembly and CCC DNA formation.
