Antiviral treatment of hepatitis B virus-transgenic mice by a marine organism, Styela plicata.
OBJECTIVE
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 (F(12wk) = 88.81, P(12wk) = 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 (F(12wk) = 20.71, P(12wk) = 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 (t(8wk) = -16.51, P(8wk) = 0.000<0.01). Compared with the serum levels of IL-2 in the normal diet-treated mice (2.48+/-0.17 ng/L; t(8wk) = 13.23, P(8wk) = 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.


CONCLUSIONS
Styela plicata may be an effective antiviral medicine in treating chronic hepatitis B.
Wang
Rui
R
Research Center for Pharmaceutics, Southern Medical University, Guangzhou 510315, Guangdong Province, China.
Du
Zhen-Lan
ZL
Duan
Wen-Jun
WJ
Zhang
Xin
X
Zeng
Fan-Lin
FL
Wan
Xin-Xiang
XX
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D019259:Lamivudine / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D014020:Tissue Extracts / Q000627:therapeutic use*; D014561:Urochordata
D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D007376:Interleukin-2; D015850:Interleukin-6; D014020:Tissue Extracts; D019259:Lamivudine