Sanguisorba officinalis extract, ziyuglycoside I, and II exhibit antiviral effects against hepatitis B virus

Introduction: Sanguisorba officinalis (SO) has been commonly used to relieve dermatitis, burns, intestinal infections, hematemesis, and melena for a long time in China, Korea, and Japan. The aim of this study was to investigate the antiviral effects of 30% ethanol extract of SO (SOE) and its major compounds (ziyuglycoside I and II) against HBV in HepG2.2.15 cells and HepG2 cells transfected with HBV genotype C. Methods: The antiviral activities of SOE were evaluated by ELISA and quantitative RT-PCR assay in in vitro models. In addition, its effect on HBsAg level was compared to entecavir (ETV), and its co-treatment with ETV was performed to observe combination efficacy. After HPLC analysis of ziyuglycoside I and II, the effects of those compounds on HBsAg levels were measured. Results: SOE, ziyuglycoside I, and II significantly reduced HBsAg excretion and the pgRNA levels in HepG2.2.15 cells. In particular, SOE treatment of 100 μg/ml showed an inhibitory effect on HBsAg excretion similar to the levels found with ETV treatment of the same concentration. Additional use of 125 μg/ml of SOE in combination with 80 μM of ETV inhibited HBsAg production up to the level that is diminished by 320 μM ETV treatment in HepG2.2.15 cells. Among SOE, ziyuglycoside I, II, and ETV, ziyuglycoside II had the lowest inhibitory concentration of 50% against genotype D, and it was more potent against HBV genotype C than D in down-regulating HBsAg secretion. Conclusion: Taken together, SOE noticeably inhibited replication and antigen secretion of HBV, which was at least in part attributed to ziyuglycoside II, thus presenting the possibility of developing therapeutic candidates for the treatment of HBV-related diseases.