The Hepatitis B virus (HBV) infection is a critical public health problem due to its detrimental effects on the liver, leading to the development of liver cirrhosis and hepatocellular carcinoma. If hepatitis persists, it may progress to chronic hepatitis, cirrhosis, and even liver cancer (hepatocellular carcinoma). A vaccine for hepatitis B is available, yet it comes with a range of side effects, with emphasis placed on the potential occurrence of shock or anaphylaxis within 30 minutes post-vaccination. However, fucoidan stands in stark contrast as a natural sulfated polysaccharide sourced from different forms of wakame seaweed. This unique compound has gained attention for its ability to manifest a multitude of physiological activities, all while being considered a safe and side effect-free substance. The effect of fucoidan on HBV is currently unknown.
So, then I would like to inform of you the study, “Fucoidan from Fucus vesiculosus suppresses hepatitis B virus replication by enhancing extracellular signal-regulated Kinase activation” by Huifang LiL. One of the main aspects of their study was to determine if fucoidan could effectively inhibit HBV replication in vivo. C57BL/6 mice were hydrodynamically injected with 10 μg of pHBV1.3 plasmid. On the other hand, mice were intraperitoneally administered 100 mg of fucoidan on days 0, 1, 3, 5, and 7 after the onset of infection. As shown in Figure 1a, serum HBV DNA levels were significantly reduced after fucoidan injection. Additionally, Fucoidan administration also suppressed the secretion of HBsAg and HBeAg. (See Figure. 1b) The immunohistochemical analysis conducted on the liver tissues of HBV-infected mice demonstrated that fucoidan exhibited a suppressive effect on HBcAg expression. (See Figure. 1d) These results indicated that fucoidan could inhibit HBV replication in vivo.
Additionally, the CCK8 assay indicated that fucoidan exhibited no cytotoxicity towards HepG2.2.15 cells when administered at concentrations below 200 μg/ml. Real-time PCR revealed that fucoidan treatment reduced the levels of HBV DNA replication intermediates in a dose-dependent manner. (See Figure. 2b) Fucoidan treatment was followed by Northern blotting to gauge intracellular HBV RNA levels. The results showed that treatment with different concentrations of fucoidan induced a dose-dependent decrease in HBV RNA levels in HepG2.2.15 cells. Western blotting analysis indicated a substantial decrease in HBsAg and HBcAg expression in HepG2.2.15 cells upon treatment with fucoidan. (See Figure. 2g)
Western blotting also showed that Fucoidan treatment significantly restricted the expression of HBV core protein in HBV-infected HepG2 cells. The collective data strongly indicates that fucoidan has the potential to inhibit HBV replication in vitro.
In order to assess the potential of Fucoidan to regulate type I interferon responses, we investigated its impact on the activation of interferon regulatory factor 3 (IRF3) and IRF7 in HepG2.2.15 cells. The results showed that fucoidan significantly promoted the phosphorylation of IRF3 and IRF7 in HBV-transfected cells. (See Figure. 3b) Fucoidan also enhanced IFN-α production at both mRNA and protein levels. While the serum samples from control mice displayed elevated levels of IFN-α, the serum samples from HBV-infected mice treated with fucoidan exhibited decreased levels of this cytokine. The results indicated that fucoidan selectively activated the HERK pathway, leading to an enhanced HER type I interferon response both in vitro and in vivo.
After ERK inhibition, Fucoidan-mediated enhancement of IFN-α expression was significantly inhibited at either the mRNA or protein level. The levels of HBV-DNA and secretion of HBsAg and HBeAg in culture supernatants were equivalent between control cells and cells treated with fucoidan with U0126 pretreatment. Data showed that Fucoidan-mediated HBV replication inhibition was prevented after pretreatment with an ERK inhibitor. The results clearly demonstrated that the inhibition of HBV by fucoidan relied on the activation of ERK.
Therefore, based on the findings of this study, it can be concluded that fucoidan exerts inhibitory effects on HBV replication in both in vivo and in vitro settings. By activating the ERK signaling pathway, fucoidan effectively suppresses HBV gene expression and enhances the production of type I interferon, as indicated by the study’s findings. This novel mechanism suggests the possibility of an alternative approach to inhibit HBV replication. In addition, fucoidan by itself or in conjunction with other established anti-HBV medications could potentially be utilized as an innovative therapeutic approach for the prevention and treatment of HBV.
Source: Virol J. 2017; 14: 178. doi: 10.1186/s12985-017-0848-8