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World J Gastroenterol. Jul 7, 2006; 12(25): 4038-4043
Published online Jul 7, 2006. doi: 10.3748/wjg.v12.i25.4038
Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism, Styela plicata
Rui Wang, Zhen-Lan Du, Wen-Jun Duan, Xin Zhang, Fan-Lin Zeng, Xin-Xiang Wan
Rui Wang, Wen-Jun Duan, Xin Zhang, Fan-Lin Zeng, Xin-Xiang Wan, Research Center for Pharmaceutics, Southern Medical University, Guangzhou 510315, Guangdong Province, China
Zhen-Lan Du, Hematopoietic Stem Cell Transplantation, 307 Hospital, Academy of Military Medical Sciences, Beijing 100039, China
Co-first-author: Zhen-Lan Du
Supported by the Social Development Program of Department of Science and Technology of Guangdong Province, No. 2004B30101009
Correspondence to: Professor Xin-Xiang Wan, Research Center for Pharmaceutics, Southern Medical University, Guangzhou 510315, Guangdong Province, China. wxx505380@126.com
Telephone: +86-20-61650526 Fax: +86-20-61650516
Received: January 12, 2006
Revised: February 8, 2006
Accepted: February 18, 2006
Published online: July 7, 2006
Abstract

AIM: To evaluate the antiviral effect of the effective ingredient of Styela plicata in a murine model of hepatitis B virus carrier.

METHODS: HBV-transgenic mice were divided into 3 groups (control group, lamivudine treatment group and the effective ingredient of Styela plicata treatment group) and assigned to receive normal diet, lamivudine or the effective ingredient of Styela plicata for consecutive weeks. Serum hepatitis B surface antigen was detected by enzyme-linked immunosorbent assay (ELISA) method. Serum HBV DNA was detected by real-time polymerase chain reaction (RT-PCR). Serum T helper (h) 1 cytokine interleukin (IL)-2 and Th2 cytokine IL-6 were detected by the quantitative sandwich enzyme immunoassay technique. Another group of HBV-transgenic mice was assigned to receive the effective ingredient of Styela plicata for consecutive weeks. The histology of liver tissue was evaluated before and after treatment.

RESULTS: Twelve weeks after starting the therapy, serum hepatitis B surface antigen was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet (F12wk = 88.81, P12wk = 0.000 < 0.01). Serum HBV DNA was significantly lowered in Styela plicata -treated mice and lamivudine-treated mice compared with the mice receiving normal diet (F12wk = 20.71, P12wk = 0.000 < 0.01). However, like lamivudine, the effective ingredient of Styela plicata could not inhibit the replication of HBV completely. A rebound phenomenon of hepatitis B surface antigen and HBV DNA in sera could be found 4 wk after withdrawal of medication. Eight weeks after starting the therapy, serum levels before and after Styela plicata treatment of IL-2 were 2.41 ± 0.38 and 10.56 ± 0.78 ng/L, respectively (t8wk = -16.51, P8wk = 0.000 < 0.01). Compared with the serum levels of IL-2 in the normal diet-treated mice (2.48 ± 0.17 ng/L; t8wk = 13.23, P8wk = 0.000 < 0.01). Serum levels before and after Styela plicata treatment of IL-6 were 63.62 ± 6.31 and 54.52 ± 6.22 ng/L, respectively, compared with the serum levels of IL-6 in the normal diet-treated mice (60.84 ± 4.21 ng/L). Histological analysis of liver from Styela plicata-treated HBV-transgenic mice also showed catabatic status in inflammation and hepatitis B surface antigen.

CONCLUSION: Styela plicata may be an effective antiviral medicine in treating chronic hepatitis B.

Keywords: Styela plicata; Hepatitis B virus; Transgenic mice; RT-PCR; Chronic hepatitis B