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Acta Pharm Sin B. 2017 May;7(3):311-318. doi: 10.1016/j.apsb.2017.02.005. Epub 2017 May 2.

T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model.

Author information

1
Chengde Medical College, Chengde 067000, China.
2
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China.
3
Integrative Medical Center, 302 Military Hospital, Beijing 100039, China.
4
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
5
Research Center for Clinical & Translational Medicine, 302 Military Hospital, Beijing 100039, China.
6
Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.

Abstract

Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV) in vitro, limited research has been done with this drug in vivo. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon-γ (IFN-γ) in a dose-dependent manner in CD4+ T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.

KEYWORDS:

ALT, alanine aminotransferase; AST, aspartate aminotransferase; CD4+ T cell; CHB, chronic hepatitis B; ETV, entecavir; HBV; HBV, hepatitis B virus; HBcAg, hepatitis B core antigen; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HE, hematoxylin and eosin; IFN-γ; IFN-γ, interferon-γ; IL-4, interleukin-4; Mouse; NAs, nucleoside and nucleotide analogs; OMT, oxymatrine; Oxymatrine; TCMs, traditional Chinese medicines; TNF-α, tumor necrosis factor-α

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