Combining Oxymatrine or Matrine with Lamivudine Increased Its Antireplication Effect against the Hepatitis B Virus In Vitro

Some recent clinical reports have shown that the combination of oxymatrine, a phyto-derived drug, with lamivudine (3TC) could improve its curative effect against hepatitis B virus (HBV) infection. However, the experimental data in support of this combination strategy are lacking. In this study, we investigated the anti-HBV activity of the combination of 3TC and either oxymatrine or matrine on HepG2 2.2.15 in vitro. The activities of the combination and the solo compound, each in different concentrations, were compared on the 3rd, 6th, and 9th experimental days. The cytotoxicity results showed that the nontoxic concentrations of both oxymatrine and matrine to HepG2 2.2.15 cells were 800 mu g/mL. We found that the single use of oxymatrine below 100 mu g/ml, matrine below 200 mu g/ml, and 3TC below 30 mu g/ml showed weak inhibitory effects on the secretion of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV-DNA in culture media; the combination of 3TC (30 mu g/ml) with oxymatrine (100 mu g/ml) or matrine (100 mu g/ml) showed significant inhibitory effects that were higher than or equivalent to the single use of 3TC at 100 mu g/ml. The results provide a new impetus to develop novel, multicomponent anti-HBV drugs through the combination of natural products with nucleoside analogs to enhance their activity.