Anti-HBV Activities of Polysaccharides from Thais clavigera (Küster) by In Vitro and In Vivo Study.

Fei Tang,Guanghua Huang,Xiuling Cui,Hong Yin,Lili Shao,Liping Lin,Ruian Xu

doi:10.3390/md19040195

Abstract

Hepatitis B virus (HBV) infection remains a major global health problem. It is therefore imperative to develop drugs for anti-hepatitis B with high-efficiency and low toxicity. Attracted by the observations and evidence that the symptoms of some patients from the Southern Fujian, China, suffering from hepatitis B were alleviated after daily eating an edible marine mollusk, Thais clavigera (Küster 1860) (TCK). Water-soluble polysaccharide from TCK (TCKP1) was isolated and characterized. The anti-HBV activity of TCKP1 and its regulatory pathway were investigated on both HepG2.2.15 cell line and HBV transgenic mice. The data obtained from in vitro studies showed that TCKP1 significantly enhanced the production of IFN-α, and reduced the level of HBV antigens and HBV DNA in the supernatants of HepG2.2.15 cells in a dose-dependent manner with low cytotoxicity. The result of the study on the HBV transgenic mice further revealed that TCKP1 significantly decreased the level of transaminases, HBsAg, HBeAg, and HBV DNA in the serum, as well as HBsAg, HBeAg, HBV DNA, and HBV RNA in the liver of HBV transgenic (HBV-Tg) mice. Furthermore, TCKP1 exhibited equivalent inhibitory effect with the positive control tenofovir alafenamide (TAF) on the markers above except for HBV DNA even in low dosage in a mouse model. However, the TCKP1 high-dose group displayed stronger inhibition of transaminases and liver HBsAg, HBeAg, and HBV RNA when compared with those of TAF. Meanwhile, inflammation of the liver was, by pathological observation, relieved in a dose-dependent manner after being treated with TCKP1. In addition, elevated levels of interleukin-12 (IL-12) and interferon γ (IFN-γ), and reduced level of interleukin-4 (IL-4) in the serum were observed, indicating that the anti-HBV effect of TCKP1 was achieved by potentiating immunocyte function and regulating the balance of Th1/Th2 cytokines.

Highlights

Despite the popularization of a safe and effective vaccine against hepatitis B virus (HBV), HBV infection remains a major global health problem with 257 million people being chronically infected worldwide [1]
The results showed that the inhibition activity of TCKP1 on HBV DNA synthesis in vivo increased with dose, but was slightly lower than that of tenofovir alafenamide (TAF) (Figure 4A)
Thais clavigera (Küster) (TCK), a popular edible conch from the Southeast China sea, we launched a systematical investigation into the anti-HBV effect of this species

Summary

Introduction

Despite the popularization of a safe and effective vaccine against hepatitis B virus (HBV), HBV infection remains a major global health problem with 257 million people being chronically infected worldwide [1]. One-third of these carriers are projected to develop severe end-stage liver diseases including liver failure, cirrhosis, and hepatocellular carcinoma (HCC), and over 887,000 people die from these liver diseases caused by HBV infection per year [2,3,4]. There are some anti-HBV drugs available today, such as interferon-α (IFN-α), the nucleoside analogues, e.g., lamivudine (3TC), adefovir dipivoxil, and tenofovir alafenamide (TAF). Many polysaccharides from plants have been shown to possess excellent anti-HBV activities [13,14]. A few polysaccharides from marine creatures, polyguluronate sulfate, scallop polysaccharide, for instance, have been found with considerable anti-HBV activity on HepG2.2.15 cells [15,16,17,18]. The precise function and mechanism of these polysaccharides in anti-HBV activity in vivo are still unknown

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