Thumbnail
Access Restriction
Open

Author Huang, Hai
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ DNA ♦ DNA REPLICATION ♦ DRUGS ♦ HEPATITIS ♦ LIVER CELLS ♦ MUTANTS ♦ MUTATIONS ♦ NUCLEOSIDES ♦ POLYMERASE CHAIN REACTION ♦ PROTEINS ♦ RNA ♦ THERAPY ♦ TRANSCRIPTION ♦ VIRUSES
Abstract Background: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. Objectives: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. Methods: The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. Results and discussion: BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV{sup rtM204V/rtLl80M} transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1 kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. - Highlights: • Baicalin benefits the anti-HBV therapy. • Baicalin enhances ETV antiviral efficacy and overcomes NA-resistant HBV mutation. • The anti-HBV effect of baicalin is achieved by inhibiting HBV RNAs. • Baicalin down-regulates HBV replication-dependent host factors HNF 1α and HNF 4α.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2017-05-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 323


Open content in new tab

   Open content in new tab