Anti-hepatitis B virus activities of α-DDB–FNC, a novel nucleoside–biphenyldicarboxylate compound in cells and ducks, and its anti-immunological liver injury effect in mice

Abstract

Infection with hepatitis B virus (HBV) continues to be a major global cause of acute and chronic liver disease with high mortality. Herein, we examined both the anti-HBV and hepatoprotective activity of α-DDB–FNC. In human HBV-transfected liver cell line HepG2.2.15, α-DDB–FNC effectively suppressed the secretion of HBV antigens in a time and dose-dependent manner with 25.11% inhibition on HBeAg and 43.68% on HBsAg at 2.5μM on day 9. Consistent with the HBV antigen reduction, α-DDB–FNC (2.5μM) also reduced HBV DNA level by 77.74% extracellularly and 78.94% intracellularly on day 9. In the duck hepatitis B virus (DHBV) infected ducks, after α-DDB–FNC was given once daily for 10days, the serum and liver DHBV DNA levels were reduced markedly with 96.81% and 97.21% at 10mgkg−1 on day 10, respectively. In Con A-induced immunological liver-injury mice, α-DDB–FNC significantly inhibited the elevation of serum ALT, AST, TBiL and liver MDA, NO levels. Furthermore, significant improvement of the liver was observed after α-DDB–FNC treatment both in ducks and mice, as evaluated by the histopathological analysis. In conclusion, our results demonstrated that α-DDB–FNC possesses both antiviral activity against HBV and hepatoprotective effect to Con A-induced liver-injury mice.