Oxymatrine inhibits hepatitis B infection with an advantage of overcoming drug-resistance.

Abstract

Oxymatrine (OMTR) is an anti-hepatitis drug used in China. Its mechanism of action is unknown. Recently, we found that OMTR inhibits hepatitis B virus (HBV) via down-regulating the expression of heat-stress cognate 70 (Hsc70), a host protein required for HBV DNA replication. Goal of this study was to assess the effect of OMTR on clinical HBV drug-resistance. OMTR monotherapy (oral, 12 months) reduced blood HBV DNA by 96% and HBeAg by 70% in the chronic hepatitis B (CHB) patients resistant to lamivudine (n = 17), equal to its efficacy in the naïve CHB cohort (n = 20). Liver biopsy study showed that OMTR treatment caused a decrease of Hcs70 mRNA in liver cells, parallel with a reduction of intracellular HBV DNA. Combination of lamivudine with OMTR (n = 15) (oral, 12 months) showed an enhanced anti-HBV effect as compared to lamivudine monotherapy (n = 25). The incidence of drug resistance against lamivudine in the combination group was significantly lower than that in the lamivudine group (1/15 vs 7/25; p<0.01). The results were further confirmed in vitro. Treatment of HBV(+) HepH2215 cells with sub-optimal dose of OMTR for 8 months suppressed HBV replication without inducing drug resistance, whereas lamivudine monotherapy caused drug-resistant mutation in 3 months. Combination of OMTR with lamivudine prevented HBV from developing drug resistance.

• Authors: Yu-Ping Wang, Wei Zhao, Rong Xue, Zhen-Xian Zhou, Fei Liu, Yan-Xing Han, Gang Ren, Zong-Gen Peng, Shan Cen, Hong-Shan Chen, Yu-Huan Li, Jian-Dong Jiang
• Journal: Antiviral research (Antiviral Res) Vol. 89 Issue 3 Pg. 227-31 (Mar 2011) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 21277330 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Alkaloids
• Antiviral Agents
• DNA, Viral
• HSC70 Heat-Shock Proteins
• HSPA8 protein, human
• Hepatitis B e Antigens
• Quinolizines
• Lamivudine
• oxymatrine

Topics

• Administration, Oral
• Adult
• Alkaloids (administration & dosage, pharmacology)
• Antiviral Agents (administration & dosage, pharmacology)
• Biopsy
• China
• DNA, Viral (blood)
• Down-Regulation
• Drug Resistance
• Drug Therapy, Combination
• Female
• Gene Expression Profiling
• HSC70 Heat-Shock Proteins (biosynthesis)
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (drug effects)
• Hepatitis B, Chronic (drug therapy)
• Humans
• Lamivudine (administration & dosage)
• Liver (pathology)
• Male
• Middle Aged
• Quinolizines (administration & dosage, pharmacology)
• Treatment Outcome
• Viral Load