Geng Tao Liu Pages 29 - 43 ( 15 )
Chronic viral hepatitis B and C are diseases worldwide. At present, the number of effective and safe drugs for treatment of HBV and HCV is still limited. In order to develop novel anti-viral hepatitis drug, a number of analogues of the active component schizandrin C from Fructus Schiznadrae, a Chinese herb used in the therapy of viral hepatitis, were synthesized. Bicyclol, one of the analogues, was demonstrated to have actions of anti-hepatitis virus replication in duck hepatitis model and 2.2.15 cell line, anti-experimental liver injury induced by hepatotoxins such as CCl4, acetaminophen and ConA, and anti-liver fibrosis in rats and mice. The active mechanism of bicyclol might be anti-apoptosis of hepatocytes through multiple signaling pathways mainly inducing the expressions of hepatic heat shock proteins (HSP27 and HSP70), molecular chaperons. Clinical trial was performed by double blind, randomized and positive control or placebo method in multi-medical centers in China. Patients received bicyclol 25mg thrice daily for six months, then stopped treatment and followed up for 3 months. Oral administration of bicyclol normalized the elevated serum transaminases (ALT, AST) by approximately 50% in chronic viral hepatitis B and C, and also showed certain level of inhibiting HBV and HCV replication. No noticeable adverse reaction has been observed. In combination therapy of bicyclol with interferon alpha, lamivudine and adefovir dipivoxil in HBV or HCV, bicyclol may potentiate the anti-viral efficacy and reduce YMDD mutant and side effects. In 2004 China FDA issued license to manufacture bicyclol. Since then bicyclol has been widely used to treat chronic HBV and HCV in China.
Chronic viral hepatitis, new drug, bicyclol, apoptosis, combination therapy, pegylated interferon, lamivudine, adefovir
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China.