Prophylactic Effect of Dietary Seaweed Fucoidan against Enteral Prion Infection

Abstract

Dietary seaweed fucoidan delays the onset of disease of enterally infected mice with scrapie when given orally for 6 days after infection, but not when given before the infection. This effect was not modified at a tested fucoidan dose range and appeared to reach the maximum level at a concentration of 2.5% or less in feed. Daily uptake of fucoidan might be prophylactic against prion diseases caused by ingestion of prion-contaminated materials, although further evaluation of its pharmacology remains to be done.Transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker syndrome in humans and scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease in animals. Recent outbreaks of BSE and variant CJD (vCJD), both of which are considered to occur through ingestion of BSE-contaminated materials (reviewed in reference 21), have necessitated the development of preventive measures against these diseases.Sulfated polysaccharides, such as heparin, dextran sulfate, and pentosan polysulfate (PPS), are known either to prolong incubation periods in animals with prion diseases or to inhibit formation of pathogen-related abnormal prion protein (PrP) in prion-infected cells (reviewed in reference 3). Their therapeutic effects are attributed to inhibition of the conversion of normal PrP to abnormal PrP by either competitively binding to the normal PrP (4) or reducing normal PrP on the cell surface through stimulation of endocytosis (20). These large-molecule compounds are not taken up well from the gut to blood or from blood to the brain (a target organ of prion diseases). Therefore, these compounds are effective in cases of peripheral infection when given intraperitoneally, intravenously, or subcutaneously (8) and even in cases of intracranial infection when given intracerebroventricularly (5). Recently, PPS intracerebroventricular injection has been utilized for clinical trials of patients; the clinical outcome remains to be determined (17).Fucoidans, complex sulfated fucosylated polysaccharides, are known to have various biological activities: anticoagulant, antiviral, antiparasital, anti-inflammatory, contraceptive, and so on, because of their ability to imitate patterns of sulfate substitution on glycosaminoglycans and other sulfated glycans (2). Some fucoidans are present in large quantities in dietary brown seaweed food products, which are eaten frequently in Asian countries (9). Here, we report that fucoidan from popularly eaten brown algae has antiprion activity and delays disease onset when it is ingested after the enteral prion infection.Fucoidan was prepared from the brown seaweed Cladosiphon okamuranus Tokida (Fig. 1A) and subsequently tested as described previously (15). Briefly, the brown seaweed was suspended in distilled water adjusted to pH 3.0 with 30% HCl and heated at 100°C for 30 or 60 min. The suspension was centrifuged (10,000 ϫ g) at room temperature, and the supernat...

Heparinase I-specific disaccharide unit of heparin is a key structure but insufficient for exerting anti-prion activity in prion-infected cells

“…Conversely, GAGs always show inhibitory activities against abnormal PrP formation in prion-infected cells [8], presumably by blocking PrP interaction with endogenous GAGs [9] or by decreasing the cell surface PrP content [10]. GAGs and polyanionic glycans also effectively prolong the incubation time of the disease in peripherally prion-infected animal models [11,12]. Particularly, pentosan polysulfate, a highly sulfated polysaccharide administered into the cerebral ventricles to bypass the bloodebrain barrier [13] has been used in clinical trials for prion disease [14,15].…”

Orally Administered Amyloidophilic Compound Is Effective in Prolonging the Incubation Periods of Animals Cerebrally Infected with Prion Diseases in a Prion Strain-Dependent Manner

“…More than three independent assays were performed in each experiment. The cell surface level of cellular PrP was assayed using flow cytometry, as described previously (10). Briefly, N2a cells dispersed by treatment with 0.1% collagenase (Wako Pure Chemical Industries Ltd., Osaka, Japan) were washed with ice-cold 0.5% fetal calf serum in PBS and incubated with SAF83 (1:500) or isotype-matched control immunoglobulin G1 for 20 min on ice.…”

Assessment of Prospective Preventive Therapies for Chronic Wasting Disease in Mule Deer

“…From a population management standpoint, compounds that prevent or clear peripheral infection will be more useful than those targeting the central nervous system; from a practical standpoint, such compounds will likely need to be effective when delivered orally. Of the various prospects identified thus far, the large-molecule compounds like sulfated poly-saccharides and sulfated fucosylated poly-saccharides (Doh-ura et al, 2007), alone or in combination (Sim and Caughey, 2010), seem most promising for application to captive and free-ranging cervids. Seaweed fucoidan may deserve further attention in light of its apparent effects in delaying onset of scrapie in orally inoculated mice (Doh-ura et al, 2007).…”