Total saponins extracted from Abrus cantoniensis Hance suppress hepatitis B virus replication in vitro and in rAAV8-1.3HBV transfected mice

Hepatitis B, an infectious disease caused by hepatitis B virus (HBV), is still a serious problem affecting global public health. Abrus cantoniensis Hance (AC), a traditional Chinese medicinal herb, has been used as a folk medicine for treating hepatitis in China from ancient times. However, its active ingredients are still unclear. Our previous study indicated that saponins extracted from AC (ACS) were the active anti-HBV ingredients in AC. This study aimed to further investigate the anti-HBV effect of ACS in vitro and in vivo. HepG2.2.15 cells which consecutively produce HBV DNA and HBV antigens were used for in vitro test, and C57BL/6 mice infected by a recombinant adeno-associated virus 8 vector carrying 1.3 copies of HBV genome (rAAV8-HBV1.3) were used for in vivo test. The histopathological changes and the immune indices were evaluated in mice model. Genechip was conducted to identify genes and pathways regulated by ACS in HepG2.2.15 cells. In this study, we confirmed that ACS treatment prominently inhibited production of HBV DNA, Hepatitis Be Antigen (HBeAg), and Hepatitis B surface antigen (HBsAg) in HepG2.2.15 cells. ACS treatment also decreased serum HBsAg, HBeAg, and HBV DNA level in rAAV8-1.3HBV transfected mice, which is in accordance with the in vitro results. Moreover, HBV infection-induced liver inflammation was significantly relieved by ACS, which could be observed in H&E staining and immunohistochemistry of HBcAg. ACS treatment elevated IFN-γ level in mice serum and increased CD4+ T cell percentage in splenocytes. KEGG pathway analysis showed that phenylalanine metabolism pathway and tyrosine metabolism pathway were greatly regulated by ACS treatment. ACS exerted potent inhibitory effects on HBV replication both in vivo and in vitro, which may provide basis for its potential clinical usage.