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. 2018 Sep 6;18(1):248.
doi: 10.1186/s12906-018-2316-4.

Epigallocatechin gallate inhibits hepatitis B virus infection in human liver chimeric mice

Yu-Heng Lai  1 , Cheng-Pu Sun  2 , Hsiu-Chen Huang  3 , Jui-Chieh Chen  4 , Hui-Kang Liu  5   6 , Cheng Huang  7   8
Affiliations

Epigallocatechin gallate inhibits hepatitis B virus infection in human liver chimeric mice

Yu-Heng Lai et al. BMC Complement Altern Med. .

Abstract

Background: Persistent hepatitis B virus (HBV) infection causes liver cirrhosis and hepatocellular carcinoma and constitutes a major worldwide health problem. Currently, anti-HBV drugs are limited to peginterferon and nucleos(t)ide analogs, which are costly and have considerable side effects; the development of novel, effective anti-HBV agents is crucial.

Methods: Catechins are a major group of compounds found in green tea extract and epigallocatechin gallate (EGCG) has been shown to have antiviral properties, including inhibition of cellular entry by HBV. FRG (Fah-/-/ Rag2-/-/ IL-2Rγ/-) mice were used in this study to generate chimeras carrying human primary hepatocytes, to facilitate investigation of the inhibitory effect of EGCG on HBV infection.

Results: Here, we show the inhibitory effect of EGCG on HBV infection and replication in HuS-E/2 cells. The inhibitory effect of EGCG on HBV infection in vivo was confirmed by monitoring HBV DNA and HBsAg in serum and immunostaining the liver tissues of the human liver chimeric mice.

Conclusions: The effects of EGCG suggest a robust strategy for the treatment of HBV infection and EGCG may have therapeutic potential for the treatment of HBV-associated liver diseases.

Keywords: EGCG; HBsAg; Hepatitis B virus; Human liver chimeric mice.

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Conflict of interest statement

Ethics approval and consent to participate

All animal experiments, including mouse manipulations (e.g. dosing and bleeding), were performed under a protocol (ASIACUC permit number 14–01-637) approved by Academia Sinica Institutional Animal Care and Usage Committee (Taipei, Taiwan).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
EGCG inhibited HBV infection. DMSO-differentiated HuS-E/2 cells were infected with HBV for 20 h in the presence of EGCG and incubated for an additional 7 days. Nucleic acids were extracted from the cells and amplified to detect the presence of HBV rcDNA (a) and HBsAg mRNA (b), to evaluate the infection efficiency
Fig. 2
Fig. 2
Human albumin levels in Hu-FRG mice. The human albumin level was measured in each mouse. Data were analyzed with mean±SEM and by student t-test (HBV, n = 3; HBV + EGCG, n = 3)
Fig. 3
Fig. 3
Scheme of EGCG treatment and mouse challenge schedule
Fig. 4
Fig. 4
HBV titers in Hu-FRG mice. HBV titers were determined as HBV DNA copies (a), and HBV HBsAg expression levels (b). The data are expressed with mean±SEM and were analyzed by student t-test (HBV, n=3; HBV+EGCG, n=3; * p <0.05, ** p <0.01).
Fig. 5
Fig. 5
Expression of Fah and HBcAg in the livers of human chimeric mice. Expression of Fah and HBcAg were examined by immunofluorescence staining with antibodies against Fah and HBcAg, followed by confocal microscopy. The bars on the images represent 100 μm
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