Effects of Resveratrol on Hepatitis B Virus Replication: In vitro and in vivo Experiments

Introduction: Hepatitis B virus (HBV) infection is a disease with high incidence and lack of effective treatment. In this study, we further explored the mechanism of resveratrol (RVT) in the inhibition of HBV replication. The effects of RVT on HBV replication were verified using in vitro and in vivo experiments. Methods: HepG2 and HepG2.2.15 cell lines were cultured in vitro, and different concentrations of RVT were used to determine its effect on the proliferation of the two cell lines. Autophagy agonists and inhibitors were given, and whether RVT exerts its effect on the proliferation of HepG2 and HepG2.2.15 cells through autophagy was determined. Reverse transcription-quantitative polymerase chain reaction and Western blot were used to detect changes in autophagy-related factors LC3-II, LC3-I, Beclin 1, and p62. Through transfection of pmiR-155, shmiR-155, and the corresponding control group, the relevant mechanism of RVT in inhibiting the proliferation of HepG2 and HepG2.2.15 cells was analyzed. RVT inhibited the toxicity for HepG2.2.15 cells and reduced HBV replication in vitro (p < 0.05). This effect of RVT was enhanced by rapamycin (RAPA; autophagy activator; p < 0.05) but was partially reversed by 3-MA (autophagy inhibitor; p < 0.05). In addition, our results showed that miR-155 expression was higher in HepG2.2.15 cells than in HepG cells (p < 0.05). miR-155 expression in the RVT treatment group was significantly reduced (p < 0.05). We designed an miR-155 overexpression plasmid, low miR-155 expression plasmid, and the corresponding negative control for transfection and found that transfection of pmiR-155 can partially reverse the effect of RVT (p < 0.05), while transfection with shmiR-155 can enhance the effect of RVT (p < 0.05). Discussion: RVT inhibits miR-155, activates autophagy, inhibits the toxicity for HepG2.2.15 cells, and reduces HBV replication, providing a new research direction for the treatment of HBV infection.