A NTIMICROBIAL –A NTIVIRAL E FFECTS

5.4.2 A NTIMICROBIAL –A NTIVIRAL E FFECTS

Apart from their antitumor effects, schizophyllan and lentinan are also useful as immunostimulatory agents acting against microbial infections, such as tuberculosis (by Mycobacterium tuberculosis) and Listeria monocytogenes infection. The anti- microbial activity of lentinan is mediated by augmentation of phagocytosis of micro- bial cells by neutrophils and macrophages. 2,172,174 In a study on the microbiocidal activity of lentinan, it was found that lentinan induced activation of peritoneal macrophages against Salmonella enteritis and especially bronchoalveolar macroph- ages against Staphylococcus aureus, possibly due to adaptive transformation of the macrophages via interactions with lentinan. 187 Also, lentinan showed high antiviral activity against influenza virus, prevented proliferation of polio virus, increased host resistance to HIV virus, and limited the toxicity of AZT, a common drug used against the HIV virus. The mechanism of antiviral activity of this glucan is believed to be linked to induction of interferon. 188 Inhibition of HIV replication was also achieved by curdlan sulfate in vitro. Possibly curdlan sulfate impedes the attachment of the virus onto the host cell, although encapsulation of the virus by the glucan, after being internalized into the cell, might also occur. 189 Scleroglucan is another β-glucan with antiviral functions. It has been proposed that the mode of action of scleroglucan against herpes simplex virus (HSV) and rubella virus is based on the binding of the bioactive glucan to glycoproteins of the host cell membrane, which hinders interac- tions between the virus and the host cell plasma. However, this inhibition mechanism is only effective at an early stage of the infection, i.e., before the host cell is infected with various RNA. 190,191 In a similar study, the antiherpetic activity of an acidic protein-bound polysaccharide from Ganoderma lucidum was attributed to the bind- ing of the biomolecule with HSV-specific glycoproteins of the cell membrane, which are responsible for virus attachment and penetration. 72

Glucans from S. cerevisiae also exert significant antimicrobial effects. Particulate (but not soluble) glucan from baker’s yeast, as well as SSG-glucan from Sclerotinia

sclerotiorum , inhibited growth of Mycobacterium tuberculosis in vitro, especially when administered at the time of infection initiation. 192 Additionally, administration of 0.5 to 4.0 mg/kg dose of PGG-glucan from S. cerevisiae reduced significantly the counts of antibiotic-resistant S. aureus in the blood of contaminated mice. 193 The enhanced clearance of S. aureus by PGG is accompanied by an increase in monocytes and neutrophils, as well as a stimulation of oxidative microbicidal activity by neu- trophils. Also, when used in combination with traditional antibiotics, PGG enhanced drug effectiveness against S. aureus. 193

Schizophyllan has also shown significant antiviral activity against Sendai virus (otherwise lethal to mice) by both oral and intraperitoneal administration. 194 Also,

sizofiran, the commercial type of pharmacological schizophyllan, could stimulate the immune responses of patients against hepatitis B virus, by increasing interferon-

gamma levels, and the proliferative response of peripheral blood mononuclear cells (PBMCs). 195

Microbial Polysaccharides

Furthermore, levan (fructan) from A. levanicum was used successfully for oral immunization against pneumonia caused by P. aeruginosa. 86 Oral co-administration of 1000 μg of levan and 10 μg of cholera toxin from P. aeruginosa increased resistance of humans to pulmonary infection, by increasing levan-specific titers of serum immunoglobulin A (sIgA) in the lungs. This preventive treatment was more effective when initiated in the first hours of the hemorrhage rather than 4 days later. 86

Finally, alginate has displayed significant functions as a prebiotic and the ability to regulate partly the intestinal microflora. In studies on the dietary effect of alginate on human fecal microflora, it was shown that consumption of 10 g of sodium alginate per day raised the concentration of bifidobacteria and reduced the population of

Enterobacteriacae and the occurrence of lecithinase-negative clostridia. 98 Also, when used alone or in combination with drugs in the treatment of ulcer or gastritis, alginate suppressed the population of Helicobacter pylori and promoted intestinal biocenosis, which reduced the number of staphylococci and bacteria of the genus Proteus. 98