Biological Activity of Fungal 130Glucans

Basidiocarps from more than 600 species of Basidiomycota are claimed to have antitumour properties [122], and historically many Asian societies have harvested them for eating and preparation of traditional medicines. However, only quite recently have these antitumour properties been attributable to P-glucans and their derivatives [123]. Schizophyllan (SPG, sizofilan or sizofiran) from S. commune and lentinan from basidiocarps of Lentinus edodes are both approved in Japan for the clinical treatment of several cancers [122]. In addition, there is now well-documented evidence for the effectiveness of P-glucan in treating a range of infectious microbially mediated diseases in humans, and in lowering blood pressure and cholesterol levels in humans [124].

The antitumour and other biological activities of P-glucans could be attributed to their powerful immunomodulatory effects, affecting both our innate and adaptive immune systems. They do not attack and kill cancer or invasive microbial cells directly. Instead, because they are not synthesised by humans, our immune systems recognise them as non-self molecules and hence become stimulated [124-126]. How this happens is becoming clearer, but much is still poorly understood about the signal transduction mechanisms involved [126]. Host cells possess receptors known as 'pattern recognition receptors' to detect innately such non-self molecules [125]. Several receptors have been identified, and include dectin-1 (a lectin), with a carbohydrate recognition domain, which binds specifically to P-glucans. Other receptors thought to be involved include complement receptor 3 (C3), scavenger receptors, lactosylceramide and toll-like receptors. Several receptors may be activated by a single P-glucan [124, 126].

There is still no general agreement as to which chemical or physicochemical properties of P-glucans are most important in determining their immunomodulatory activities [122, 124, 127-129]. This may reflect an inadequate chemical characterisation of the glucan preparations used in many of these experiments, or where basidiocarps have been used as sources, contamination with other polymers during their extraction [122]. Orally administered glucans may also be chemically and/or enzymatically modified in the gut before absorption [124].

Despite these concerns, it seems clear that individual P-glucans differ markedly in their effectiveness as immunomodulators, and so it is possible to suggest, with due caution, that high biological activity may be associated with the following:

(1) A (1,3)-P-linked glycosidic backbone, since a-glucans like pullulan are biologically inactive [124].

(2) The presence of (1,6)-P-linked glycosidic and other side chains, and high branching frequency [129, 130], although the explanation for this is unclear. Furthermore, although both scleroglucan and schizophyllan have the same branching frequencies (1:3), scleroglucan has a higher receptor binding capacity than schizophyllan [131].

(3) A triple helical conformation [132], although some (1,3)(1,6)-P-glucans with triple helical arrangements are ineffective and their activity became apparent once their conformation changed from a triple helix to a single helical conformation [133, 134]. With schizophyllan, a single helical conformation gave higher biological activity than that shown by the native triple helical form [132].

(4) A high molecular weight, which might reflect the formation of triple helices, since low-molecular-weight glucans form no helices as the chains are too short [129, 135, 136].

(5) A high water solubility [129], which reflects their branching frequencies, the likelihood of triple helix formation and to some extent their DP.

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