title: 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 2.5 μM on day 9. Consistent with the HBV antigen reduction, α-DDB-FNC (2.5 μM) 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 10 days, the serum and liver DHBV DNA levels were reduced markedly with 96.81% and 97.21% at 10 mgkg(-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.
authors.affiliation: The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Yang
authors.forename: Xuejie
authors.initials: X
authors.lastname: Zhao
authors.forename: Limin
authors.initials: L
authors.lastname: Zang
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Fang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Yang
authors.forename: Qingduan
authors.initials: Q
authors.lastname: Wang
authors.forename: Liyun
authors.initials: L
authors.lastname: Zheng
authors.forename: Junbiao
authors.initials: J
authors.lastname: Chang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000473:pathology; D003208:Concanavalin A / Q000633:toxicity; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019610:Cytoprotection; D004261:DNA Replication; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004372:Ducks / Q000821:virology*; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000188:drug therapy / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000821:virology; D008297:Male; D051379:Mice; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
chemical_list: C581093:4'-azido-2'-deoxy-2'-fluoro-3'-(4,4'-dimethoxy-2'-methoxycarbonyl-5,6,5',6'-bis(methylenedioxy)-1,1'-biphenyl-2-carboxyl)cytidine; D000998:Antiviral Agents; D052117:Benzodioxoles; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D003208:Concanavalin A; D003562:Cytidine