Anti-Influenza A Virus Activity of Rhamnan Sulfate from Green Algae Monostroma nitidum in Mice with Normal and Compromised Immunity

Abstract

Influenza viruses cause a significant public health burden each year despite the availability of anti-influenza drugs and vaccines. Therefore, new anti-influenza virus agents are needed. Rhamnan sulfate (RS) is a sulfated polysaccharide derived from the green alga Monostroma nitidum. Here, we aimed to demonstrate the antiviral activity of RS, especially against influenza A virus (IFV) infection, in vitro and in vivo. RS showed inhibitory effects on viral proliferation of enveloped viruses in vitro. Evaluation of the anti-IFV activity of RS in vitro showed that it inhibited both virus adsorption and entry steps. The oral administration of RS in IFV-infected immunocompetent and immunocompromised mice suppressed viral proliferation in both mouse types. The oral administration of RS also had stimulatory effects on neutralizing antibody production. Fluorescent analysis showed that RS colocalized with M cells in Peyer's patches, suggesting that RS bound to the M cells and may be incorporated into the Peyer's patches, which are essential to intestinal immunity. In summary, RS inhibits influenza virus infection and promotes antibody production, suggesting that RS is a potential candidate for the treatment of influenza virus infections.

Biological Activities of Rhamnan Sulfate Extract from the Green Algae Monostroma nitidum (Hitoegusa)

“…RS has been reported to have biological activities such as antiviral [6,[9][10][11][12][13], anticoagulant [14][15][16][17][18][19][20][21], and antitumor [22] activities. It also induces hyaluronidase inhibition [23], exhibits anti-hypercholesterolemic effect [24,25] suppresses blood glucose elevation [26], and helps with weight control [25]; thus, M. nitidum-derived RS is considered to be involved in many activities in host defense of humans.…”

“…Anti-hyaluronidase in vitro study [23] Antitumor in vitro study [22] Anti-obesity in vivo study [25] Anti-thrombosis in vitro study [14][15][16][17][18][19][20][21], in vivo study [16,17] Antivirus in vitro study [6,[9][10][11]13], in vivo study [12,13] Anti-hypercholesterolemia in vivo study [25], human trial [24] Anti-hyperglycemia in vivo study [26], human trial [26] In what follows, we describe some of the biological activities of M. nitidum-derived RS that we have studied and reported, especially its antiviral, anti-obesity, anti-hypercholesterolemic, anti-glycemia, antithrombotic, and anti-inflammation effects.…”

“…Recently, Terasawa et al showed that RS has an antiviral effect on enveloped viruses, such as measles virus, mump virus, influenza A virus, and human corona virus, but does not affect non-enveloped viruses, such as adenovirus, poliovirus, coxsackie virus, and rhinovirus. Evaluation of the in vitro anti-influenza A virus activity of RS showed that it inhibited both virus adsorption and entry steps to Madin-Darby canine kidney (MDCK) cells [13].…”

“…RS probably binds to the influenza virus hemagglutinin (HA), which is a glycoprotein on the viral envelope and important for host cell binding. Both antiviral and immune stimulating activities of RS may contribute to the suppression of viral proliferation in vivo [13].…”

“…Although fucoidan and RS are composed of different sugars, their chemical structures are similar, so it is assumed that RS enters the blood in a similar manner. Terasawa et al showed that FITC-labeled RS colocalized with Peyer's patch M cells 30 minutes after oral administration of the RS, indicating that RS could bind to the M cells and become incorporated into Peyer's patches [13]. Microfold cells (M cells) are a part of the intestinal epithelium that is involved in the selective uptake of antigens, such as polymers and bacteria, from the gut lumen into Peyer's patches, an intestinal lymphoid tissue [57][58][59].…”