Abstract:
:This study aimed to investigate anti-HBV effect and major active compounds of Su-duxing, a medicine extracted from Chinese herbs. HBV-replicating cell lines HepG2.2.15 (wild-type) and HepG2.A64 (entecavir-resistant) were used for in vitro test. C57BL/6 mice infected by adeno-associated virus carrying 1.3 mer wild-type HBV genome were used for in vivo test. Inhibitory rates of Su-duxing (10 μg/mL) on HBV replicative intermediate and HBsAg levels were 75.1%, 51.0% in HepG2.2.15 cells and 65.2%, 42.9% in HepG2.A64 cells. The 50% inhibitory concentration of Su-duxing and entecavir on HBV replicative intermediates had 0.2-fold and 712.5-fold increase respectively for entecavir-resistant HBV compared to wild-type HBV. Su-duxing and entecavir combination showed a better anti-HBV effect than each single of agents. Mice treated with Su-duxing (45.0 mg kg-1 d-1 for 2 weeks) had 1.39 log10 IU/mL decrease of serum HBV DNA, and 48.9% and 51.7% decrease of serum HBsAg and HBeAg levels. GeneChip and KEGG analysis proposed that anti-HBV mechanisms included relief of HBx stability and viral replication, deregulation of early cell cycle checkpoints, and induction of type I interferon. Quantitative RT-PCR verified that CCNA2, ATF4, FAS and CDKN1A expression levels had significant difference between Su-duxing-treated and control groups. Six active compounds (Matrine, Oxymatrine, Chlorogenic acid, Sophocarpine, Baicalein, and Wogonin) against HBV were identified in Su-duxing. Greater anti-HBV effects were observed in some compound pairs compared to each single compound. In conclusion, Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant HBV. Its effects were associated with coordinated roles of active compounds in its composition.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Liu Y,Yao W,Si L,Hou J,Wang J,Xu Z,Li W,Chen J,Li R,Li P,Bo L,Xiao X,Lan J,Xu Ddoi
10.1016/j.antiviral.2018.04.017subject
Has Abstractpub_date
2018-07-01 00:00:00pages
39-47eissn
0166-3542issn
1872-9096pii
S0166-3542(17)30530-2journal_volume
155pub_type
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