Advance Access Publication 7 January 2008 Original Article eCAM 2010;7(2)189–195 doi:10.1093/ecam/nem180 The Anti-hepatitis B Virus Activity of Boehmeria nivea Extract in HBV-viremia SCID Mice Jia-Ming Chang 1 , Kai-Ling Huang 2 , Thomas Ta-Tung Yuan 1 , Yiu-Kay Lai2,3 and Le-Mei Hung1 1Division of Research and Development, Development Center for Biotechnology, Xizhi City, Taipei County, Taiwan 221, 2Department of Life Sciences and Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan 30013 and 3Department of Bioresources, Da-Yeh University, Changhua, Taiwan 515, R.O.C. Boehmeria nivea extract (BNE) is widely used in southern Taiwan as a folk medicine for hepato- protection and hepatitis treatment. In previous studies, we demonstrated that BNE could reduce the supernatant hepatitis B virus (HBV) DNA in HBV-producing HepG2 2.2.15 cells. In the present study, we established an animal model of HBV viremia and used it to validate the efficacy of BNE in vivo. In this animal model, serum HBV DNA and HBsAg were elevated in accordance with tumor growth. To evaluate the anti-HBV activity of BNE, HBV-viremia mice were built up after one subcutaneous inoculation of HepG2 2.2.15 tumor cells in severe combined immunodeficiency mice over 13 days. The levels of serum HBV DNA were elevated around 105–106 copies per milliliter. Both oral and intraperitoneal administration of BNE were effective at inhibiting the production of HBsAg and HBV DNA, whereas tumor growth was not affected by all test articles. Intraperitoneal administration of BNE appeared to have greater potential to inhibit serum HBV DNA levels compared with oral administration under the same dosage. Notably, reduced natural killer cell activity was also observed after high dosage of BNE administration, and this correlated with reduced serum HBV DNA. In conclusion, BNE exhibited potential anti-HBV activity in an animal model of HBV viremia. Keywords: HBsAg – HBV DNA – SCID – NK cells – folk medicine Introduction Hepatitis B is caused by hepatitis B virus (HBV) infection that is common in Asia, Africa and the Middle East. Approximately 2–5% of HBV-infected people have the potential to develop a chronic infection, and HBV carriers have elevated risk for the development of cirrhosis and hepatocellular carcinoma (1). HBV is an enveloped DNA virus of the hepadnaviridae family that contains 3.2 kb partially double-stranded circular For reprints and all correspondence: Dr Jia-Ming Chang, Division of Research and Development, Development Center for Biotechnology, 101, Ln 169, Kangning St., Xizhi City, Taipei County, Taiwan 221, R.O.C. Tel: +886-2-26956933 ext. 5102; Fax: +886-2-6615-0063; E-mail: jiaming@ntu.edu.tw genome. HBV is replicated through core protein encapsi- dation of the viral pre-genomic RNA (pgRNA) that is subsequently converted to double stranded (dsDNA) by viral reverse transcriptase/polymerase to form a nucleo- capsid. The nucleocapsid is then enveloped by the viral surface protein (2). Currently, interferon-a (acting as an immunomodulator) and the nucleoside analogs lamivu- dine (3TC), adefovir and entecavir (acting as viral reverse transcriptase/polymerase inhibitors) are drugs approved for treatment of chronic hepatitis B (3,4). Despite the synergistic effect of combination therapy of these drugs for the improvement of INF-a unresponsiveness or drug resistance in HBV-infected patients, the drug-resistant HBV variants remain a major problem in hepatitis B management (5–7). Therefore, sustained and diversified strategies for viral suppression are crucial to reduce 2008 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.