Antiviral agents from traditional Chinese medicines against hepatitis B virus.

摘要

Hepatitis B virus (HBV) infection is a public health problem worldwide. There are more than 350 million carriers of this virus in the world. Though viral replication may be suppressed temporarily by certain antiviral agents, such as lamivudine, frequent relapse upon withdrawal of treatment and emergence of viral resistance would occur. No foolproof antiviral therapy against HBV is available. Thus, the development of novel anti-HBV drugs that can be administered orally or parenterally is strongly demanded.; This research project focused on assessing the values of selected traditional Chinese medicines and natural products against HBV and identifying the antiviral components in TCM. The primary duck hepatocyte (PDH) culture assay system and the duck animal model experimentally infected with duck hepatitis B virus (DHBV) were used to evaluate the antiviral properties in vitro and in vivo, respectively. The methods of dot blot, southern blot hybridization and histopathology were used in the study. Bioassay-monitored pursuit for the active components was followed.; Screening for antiviral activities against HBV by using PDH culture assay was made on 16 Chinese medicinal herbs including Polygonum cuspidatum, Ligustrum robustum, Scutellaria baicalensis, Morus alba, Lithospermum erythrorhizon , and Paeonia moutan. One hundred and forty-three purified compounds from TCM were also evaluated. Some of them showed potent or moderate antiviral activities against DHBV. Based on these results, two Chinese medicinal herbs, Ligustrum robustum and Scutellaria baicalensis with potent antiviral activities were selected for further assessment.; It was found that four of the six flavonoids isolated from S. baicalensis, and four of the eleven glycosides, isolated from the ethanol fraction of L. robustum significantly suppressed DHBV replication in vitro. The activity of the flavonoids and glycosides may partially account for the use of the two herbs in the treatment of liver diseases. Moreover, fraction B2 from the water-soluble fraction of the ethanol portion of L. robustum at the dose of 5 g/kg showed potent anti-HBV activity in vivo in the duck animal model and had an inhibition of 45% and 50% on DHBV RT at 10 mug/ml and 100 mug/ml, respectively.; Two flavonoids, morin (IC50 = 15.8 mug/ml) and naringin (IC50 = 18.6 mug/ml) were further found to have potent antiviral properties from the screening antiviral test in vitro and in vivo. (Abstract shortened by UMI.)