wogonin and Hepatitis-B

Hepatitis B Virus is the most common cause of chronic liver disease worldwide. Currently approved agents of chronic HBV infection treatment include interferon and nucleoside analogues. However, the side effects of interferon and the viral resistance of nucleoside analogues make the current treatment far from satisfactory. Therefore, new drugs with novel structures and mechanisms are needed. Recently, a number of non-nucleoside HBV inhibitors have been obtained from natural sources or prepared by synthesis/semi-synthesis. Some of them exhibited potent anti-HBV activity with novel mechanisms. These compounds provide useful information for the medicinal chemist to develop novel non-nucleoside compounds as anti-HBV agents.

Topics: Animals; Antiviral Agents; Biological Products; Hepatitis B; Hepatitis B virus; Humans; Small Molecule Libraries

Hepatitis B induced by hepatitis B virus (HBV) remains a major public health problem worldwide. Although several antiviral drugs have been approved for hepatitis B, they cause significant dose-dependent side-effects (interferon-alpha) and drug resistance (lamivudine, etc.). Safe and potent new anti-HBV drugs are urgently needed. Traditional Chinese medicine (TCM) is an established segment of the health care system in China and widely used for hepatitis B in China and many parts of the world. Many TCMs and related active compounds have been reported that have promising and potent anti-HBV activities, including Phyllanthus, Salvia miltiorrhiza, Rheum palmatum L., Radix Astragali, oxymatrine, artemisinin and artesunate, and wogonin. Thus, TCM is a potential candidate for anti-HBV drugs. More information is needed regarding TCMs, including preparation, standardization, identification of active ingredients, and toxicological evaluation. Therefore, TCM development needs to apply advanced and interdisciplinary methodology and technology and perform further rigorously designed experimental and clinical investigations.

Topics: Alkaloids; Antiviral Agents; Artemisinins; Artesunate; Astragalus propinquus; Drugs, Chinese Herbal; Flavanones; Hepatitis B; Hepatitis B virus; Humans; Medicine, Chinese Traditional; Molecular Structure; Phyllanthus; Phytotherapy; Quinolizines; Rheum; Salvia miltiorrhiza

The traditional Chinese medicine Scutellaria radix has been used for thousands of years, mainly for the treatment of inflammatory conditions including hepatitis. The major active constituent, wogonin (WG), isolated from S. radix has attracted increasing scientific attention in recent years due to its potent biological activities. However, pharmacologic studies have primarily been focused on wogonin's anti-inflammatory and anti-cancer activities. In this study, we have investigated wogonin's anti-hepatitis B virus (HBV) activity both in vitro and in vivo. In the human HBV-transfected liver cell line HepG2.2.15, wogonin effectively suppressed the secretion of the HBV antigens with an IC(50) of 4 microg/ml at day 9 for both HBsAg and HBeAg. Consistent with the HBV antigen reduction, wogonin also reduced HBV DNA level in a dose-dependent manner. Duck hepatitis B virus (DHBV) DNA polymerase was dramatically inhibited by wogonin with an IC(50) of 0.57 microg/ml. In DHBV-infected ducks wogonin dosed i.v. once a day for 10 days reduced plasma DHBV DNA level with an ED(50) of 5mg/kg. The in vivo anti-HBV effect of wogonin in ducks was confirmed by Southern blotting of DHBV DNA in the liver. Histopathological evaluation of the liver revealed significant improvement by wogonin. In addition, in human HBV-transgenic mice, wogonin dosed i.v. once a day for 10 days significantly reduced plasma HBsAg level. Immunohistological staining of the liver confirmed the HBsAg reduction by wogonin. In conclusion, our results demonstrate that wogonin possesses potent anti-HBV activity both in vitro and in vivo. Currently, wogonin is under early development as an anti-HBV drug candidate.

Topics: Animals; Antiviral Agents; Blotting, Southern; Cell Line, Tumor; DNA, Viral; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Ducks; Female; Flavanones; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Injections, Intravenous; Liver; Mice; Mice, Transgenic; Nucleic Acid Synthesis Inhibitors; Scutellaria; Transfection