RealMaitake® Mushroom

CHEMISTRY OF β-GLUCANS

β-Glucans are heterogeneous polysaccharides of glucose polymer, consisting of a backbone of β-(1-3)-linked β-D-glucopyranosyl units with β-(1-6)-linked side chains of varying distribution and length. The activity of β-glucan depends on the molecular structure, size, branching frequency, structural modification, conformation, and solubility. It appears that the most active forms of β-glucans contain β-(1-3)(1-6) linkages (1). The structure of several biologically active β-glucans has been reported. β-Glucan from many mushrooms has a β-(1-3) backbone with shorter β-(1-6) linked branches, while β-glucan from Alcaligenes faecalis contains only β-(1-3)-glucosidic linkages (2). Schizophyllan from Schizophyllum commune and scleroglucan from Sclerotium glucanicum both have a β-(1→3) linked backbone with one β-(1→6)-glucose substitution every three backbone residues (3). Lentinan from Lentinus edodes has a β-(1→3) linked backbone and two β-(1→6) side chains every five residues (4). β-Glucan from oat and barley are linear with β-(1-4) linkage with shorter stretches of β-(1-3) (3).

Biologically active β-glucans usually have a large molecular weight. However, it is unclear whether β-glucans having intermediate or small molecular weight have biological activities, although some of them are active in vivo. Short β-glucans below 5,000-10,000 Da of molecular weight are generally inactive (5). The optimal branching frequency is suggested as 0.2 (1 in 5 backbone residues) to 0.33. Although unbranched β-glucan curdlan showed proper biological activity, chemical addition of β-(1-6) glucose residues to the curdlan backbone led to an increase in anti-tumor activity (6), as highly branched β-glucan has higher affinity for cognate receptors (7). Furthermore, soluble β-glucans appear to be stronger immunostimulators than insoluble ones. When insoluble scleroglucan is modified by sulfation or carboxymethylation, the anti-tumor activity increases (8).

Further study is still required before we will fully understand the structure-activity relationship in β-glucans. Orally administered β-glucans may be modified to smaller oligosaccharides in vivo (3). Thus, the actual β-glucans binding to the immune cell surface receptors in vivo may in fact be these smaller ones. However, there is no information on this topic to date. If we can use standardize smaller β-glucans, the biological data might be fruitful.

SUMMARY

β-Glucans are potent immunomodulators that have multiple activities such as anti-tumor and anti-infective activities. However, how β-glucan exerts these diverse biological activities is still unknown. The first step mediating β-glucan action might be immunostimulation. In particular, binding of β-glucan to specific receptors in macrophages and dendritic cells can induce the production of various cytokines, indirectly activating other immune cells such as T cells and B cells under in vivo conditions. Systemic immunostimulation might be the main route in preventing the growth of cancer cells and infective microorganisms in the host. Several β-glucan receptors in macrophages and dendritic cells, such as dectin-1 and TLRs, might play a key role in the recognition of β-glucans, but the exact signaling pathways downstream from the respective receptors and the cross-talk between them is unclear to date. If we can understand these issues in greater detail, β-glucans might be widely used in the therapy of cancer and infectious diseases.