Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials

Abstract

Glucans are part of a group of biologically active natural molecules and are steadily gaining strong attention not only as an important food supplement, but also as an immunostimulant and potential drug. This paper represents an up-to-date review of glucans (β-1,3-glucans) and their role in various immune reactions and the treatment of cancer. With more than 80 clinical trials evaluating their biological effects, the question is not if glucans will move from food supplement to widely accepted drug, but how soon.

Keywords: drug; food; glucan; immunity; infection; mushrooms; supplement.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Various aspects of the both branches of immune reactions. Reaction known to be influenced by glucan are represented in white, reactions where glucan has no confirmed effects are shown in black.

Figure 2

ERK1/2 regulate IL-10 transcription via MSK1/2 dependent and independent mechanisms. Dectin-1 is activated by complex β-glucan containing particles that induce clustering of dectin-1 at the membrane and formation of a phagocytic synapse. This leads to Syk recruitment to the ITAM like sequence in the cytoplasmic domain of dectin-1. Syk then mediates the activation of downstream signaling including the ERK1/2 and p38α MAPK cascades. Both ERK1/2 and p38α phosphorylate and activate the protein kinases MSK1 and 2. These in turn phosphorylate CREB on the IL-10 gene promoter, which stimulates IL-10 mRNA transcription. In addition, ERK1/2 also activates an MSK and p38 independent pathway that inhibits IL-10 mRNA transcription. In addition to the ERK1/2 and p38α pathways shown dectin-1 also activates NFκB that likely also plays a role in inducing IL-10 transcription. From (Elcombe et al., 2013) [50].

Figure 3

Proposed mechanisms involved in glucan/zymosan uptake and signaling in human macrophages. Zymosan particles can activate Syk via Dectin-1 engagement and via adaptor protein DAP12. Upon internalization, TLR2 recognition and cathepsin B leakage occur. In the presence of M-CSF, the expression of Dectin-1 B isoform is increased. Concomitant mechanisms of NF-κB activation might be triggered. cPLA2 is activated by Dectin-1/Syk-dependent mechanisms involving MAPK-dependent Ser-505 phosphotylation and Ca2+-dependent membrane translocation. Dotted lines indicate the steps associated with phagocytic cargo processing. Ac-H3 indicates acetylated histone 3. From (Municio et al., 2013) [51].

Figure 4

Imprime activates innate immune functions. (A) Complement activation proteins C4a, C5a, SC5b-9 in the plasma of whole blood treated with 10 μg/mL Imprime or vehicle for 30 min at 37 °C was measured by ELISA. Data represent mean ± SEM of triplicates for each treatment condition. (B) Modulation of CD11b, CD62L, CD88 and CXCR2 expression on neutrophils and monocytes post Imprime binding in whole blood was determined by flow cytometry. (C) Chemokine, IL-8 and MCP-1, production in the plasma of whole blood treated with Imprime or vehicle for 24 h at 37°C was measured by Luminex. Data represent mean ± SEM of duplicates from 3 independent experiments. (D) ROS production in 25:1 co-cultures of neutrophils (isolated from whole blood treated with 25 μg/mL Imprime or vehicle for 2 h at 37 °C) and Raji cells treated with or without 1 μg/mL rituximab was measured by luminescence-based assay. Macrophage-mediated ADCP was measured by flow cytometry after 1:1 co-incubation of macrophages (differentiated from monocytes isolated from WB treated with 25 μg/mL Imprime or vehicle for 2 h at 37 °C) with Raji cells treated with or without 1 μg/mL rituximab. Representative results are shown here from at least 3 independent experiments performed with three different donors (from Chan et al., 2016) [53].

Figure 5

Changes in salivary immunoglobulins after 30 day supplementation in children with respiratory problems. G—glucan group, C—placebo group.

Figure 6

Effects if 30 days oral administration of glucan on calprotectin and albumin levels in saliva. G—glucan group, C—placebo group.

Figure 7

Total numbers of NK cells in peripheral blood of cancer patients before and after 60 day glucan supplementation. G—glucan group, C—placebo group.