Abstract

Hepatitis B virus (HBV) infection remains a major global threat to human health worldwide. Recently, the Chinese medicines with antiviral properties and low toxicity have been a concern. In our previous study, Eupolyphaga sinensis Walker polysaccharide (ESPS) has been isolated and characterized, while its antiviral effect on HBV remained unclear. The anti-HBV activity of ESPS and its regulatory pathway were investigated in vitro and in vivo. The results showed that ESPS significantly inhibited the production of HBsAg, HBeAg, and HBV DNA in the supernatants of HepG2.2.15 in a dose-dependent manner; HBV RNA and core protein expression were also decreased by ESPS. The in vivo studies using HBV transgenic mice further revealed that ESPS (20 and 40 mg/kg/2 days) significantly reduced the levels HBsAg, HBeAg, and HBV DNA in the serum, as well as HBV DNA and HBV RNA in mice liver. In addition, ESPS activated the Toll-like receptor 4 (TLR4) pathway; elevated levels of IFN-β, TNF-α, and IL-6 in the serum were observed, indicating that the anti-HBV effect of ESPS was achieved by potentiating innate immunity function. In conclusion, our study shows that ESPS is a potential anti-HBV ingredient and is of great value in the development of new anti-HBV drugs.

Highlights

  • Hepatitis B virus (HBV) infection remains a major and serious global health problem, and with 257 million chronically infected people worldwide, HBV infection often results in acute or chronic infection and contributes to a high risk of severe liver disease including liver failure, cirrhosis, hepatocellular carcinoma (HCC), or death (Yuen et al, 2018; Likhitsup et al, 2019; Carey et al, 2020)

  • We found that Eupolyphaga sinensis Walker polysaccharide (ESPS) exhibited significant inhibitory activity on the replication of HBV in vivo and in vitro, and its antiviral activity has a time- and dosedependent effect

  • The anti-HBV activity of ESPS may be associated with appropriate activation of Toll-like receptor 4 (TLR4) signaling pathway, which results in the enhancement of I interferon and pro-inflammatory factors

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Summary

Introduction

Hepatitis B virus (HBV) infection remains a major and serious global health problem, and with 257 million chronically infected people worldwide, HBV infection often results in acute or chronic infection and contributes to a high risk of severe liver disease including liver failure, cirrhosis, hepatocellular carcinoma (HCC), or death (Yuen et al, 2018; Likhitsup et al, 2019; Carey et al, 2020). Due to the lack of drugs with sustained virological response, the number of hepatitis B patients is increasing every year (Vittal and Ghany, 2019; Higashi-Kuwata et al, 2021). More and more evidence show that HBV causes different degrees of virus replication and liver inflammation under the dual effect of host–virus, leading to congenital immune dysfunction (Luangsay et al, 2015). Virological treatment is the basis of chronic hepatitis B and other related severe liver diseases (Revill et al, 2016). More and more attention has been paid to the ESPS With Anti-HBV Activities investigation of polysaccharides, and they have been reported to have excellent anti-HBV activity (Lin et al, 2016; Yang et al, 2018)

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