Fucoidan from Fucus vesiculosus suppresses hepatitis B virus replication by enhancing extracellular signal-regulated Kinase activation

Huifang Li,Xiaoyong Zhang,Liyun Zhang,Daming Zuo,Yuan Tang,Zhanglian Xie,Lin Lin,Junru Li,Zhengliang Chen,Xiaoshan Zhao,Jia Zhou

doi:10.1186/s12985-017-0848-8

Huifang Li, Xiaoyong Zhang + Show 9 more

Open Access

https://doi.org/10.1186/s12985-017-0848-8

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Abstract

BackgroundHepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma. As the clinical utility of current therapies is limited, the development of new therapeutic approaches for the prevention and treatment of HBV infection is imperative. Fucoidan is a natural sulfated polysaccharide that extracted from different species of brown seaweed, which was reported to exhibit various bioactivities. However, it remains unclear whether fucoidan influences HBV replication or not.MethodsThe HBV-infected mouse model was established by hydrodynamic injection of HBV replicative plasmid, and the mice were treated with saline or fucoidan respectively. Besides, we also tested the inhibitory effect of fucoidan against HBV infection in HBV-transfected cell lines.ResultsThe result showed that fucoidan from Fucus vesiculosus decreased serum HBV DNA, HBsAg and HBeAg levels and hepatic HBcAg expression in HBV-infected mice. Moreover, fucoidan treatment also suppressed intracellular HBcAg expression and the secretion of the HBV DNA as well as HBsAg and HBeAg in HBV-expressing cells. Furthermore, we proved that the inhibitory activity by fucoidan was due to the activation of the extracellular signal-regulated kinase (ERK) pathway and the subsequent production of type I interferon. Using specific inhibitor of ERK pathway abrogated the fucoidan-mediated inhibition of HBV replication.ConclusionThis study highlights that fucoidan might be served as an alternative therapeutic approach for the treatment of HBV infection.

Highlights

Hepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma
We provided the evidence that fucoidan activated mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and subsequently promoted the expression of IFN-α, leading the decreased production of HBV DNA and proteins
Serum HBV DNA was analyzed by using real-time PCR, and Hepatitis B surface antigen (HBsAg)/Hepatitis B e antigen (HBeAg) levels were analyzed by using ELISA

Summary

Introduction

Hepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma. Fucoidan is a natural sulfated polysaccharide that extracted from different species of brown seaweed, which was reported to exhibit various bioactivities. It remains unclear whether fucoidan influences HBV replication or not. The infection can lead to acute and chronic hepatitis, which makes liver prone to develop cirrhosis and hepatocellular carcinoma [1]. The currently approved agents for the treatment of HBV infection include immunomodulatory agents, such as interferon-α (IFN-α) and pegylated IFN-α, and oral nucleoside/nucleotide analogues, like lamivudine, adefovir, telbivudine, entecavir and tenofovir [3, 4]. Exploring and developing new antiHBV agents different from nucleoside/nucleotide analogues and interferon are urgently needed

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