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Non-prescriptional use of medicinal herbs among cancer patients is common around the world. The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in vitro or in vivo animal experiments. The current information suggests that these herbal extracts exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of the active compounds responsible for the immune effects of herbal products is in the form of complex polysaccharides known as beta-glucans. beta-glucans are ubiquitously found in both bacterial or fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based on in vitro studies, beta-glucans act on several immune receptors including Dectin-1, complement receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages, neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and adaptive response can be modulated by beta-glucans and they can also enhance opsonic and non-opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 1-->3 linear beta-glycosidic chain of beta-glucans cannot be digested. Most beta-glucans enter the proximal small intestine and some are captured by the macrophages. They are internalized and fragmented within the cells, then transported by the macrophages to the marrow and endothelial reticular system. The small beta-glucans fragments are eventually released by the macrophages and taken up by other immune cells leading to various immune responses. However, beta-glucans of different sizes and branching patterns may have significantly variable immune potency. Careful selection of appropriate beta-glucans is essential if we wish to investigate the effects of beta-glucans clinically. So far, no good quality clinical trial data is available on assessing the effectiveness of purified beta-glucans among cancer patients. Future effort should direct at performing well-designed clinical trials to verify the actual clinical efficacy of beta-glucans or beta-glucans containing compounds.
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BioMed Central
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Journal of Hematology & Oncology
Open Access
The effects of β-glucan on human immune and cancer cells
Godfrey Chi-Fung Chan*1, Wing Keung Chan1 and Daniel Man-Yuen Sze2
Address: 1Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong and
2Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong
Email: Godfrey Chi-Fung Chan* -; Wing Keung Chan -; Daniel Man-
Yuen Sze -
* Corresponding author
Non-prescriptional use of medicinal herbs among cancer patients is common around the world.
The alleged anti-cancer effects of most herbal extracts are mainly based on studies derived from in
vitro or in vivo animal experiments. The current information suggests that these herbal extracts
exert their biological effect either through cytotoxic or immunomodulatory mechanisms. One of
the active compounds responsible for the immune effects of herbal products is in the form of
complex polysaccharides known as β-glucans. β-glucans are ubiquitously found in both bacterial or
fungal cell walls and have been implicated in the initiation of anti-microbial immune response. Based
on in vitro studies, β-glucans act on several immune receptors including Dectin-1, complement
receptor (CR3) and TLR-2/6 and trigger a group of immune cells including macrophages,
neutrophils, monocytes, natural killer cells and dendritic cells. As a consequence, both innate and
adaptive response can be modulated by β-glucans and they can also enhance opsonic and non-
opsonic phagocytosis. In animal studies, after oral administration, the specific backbone 13 linear
β-glycosidic chain of β-glucans cannot be digested. Most β-glucans enter the proximal small
intestine and some are captured by the macrophages. They are internalized and fragmented within
the cells, then transported by the macrophages to the marrow and endothelial reticular system.
The small β-glucans fragments are eventually released by the macrophages and taken up by other
immune cells leading to various immune responses. However, β-glucans of different sizes and
branching patterns may have significantly variable immune potency. Careful selection of appropriate
β-glucans is essential if we wish to investigate the effects of β-glucans clinically. So far, no good
quality clinical trial data is available on assessing the effectiveness of purified β-glucans among cancer
patients. Future effort should direct at performing well-designed clinical trials to verify the actual
clinical efficacy of β-glucans or β-glucans containing compounds.
A significant proportion of cancer patients have been tak-
ing complementary medical therapies while receiving
their conventional anti-cancer treatments [1-6]. Among
them, herbal extracts such as Ganoderma lucidum are one
of the most common modalities being consumed espe-
cially among Oriental [7-10]. Two mechanisms have been
proposed to be responsible for the anti-cancer action of
these herbal extracts; one is via direct cytotoxic effect and
the other is indirectly through immunomodulatory action
[11,12]. Many cytotoxic chemotherapeutic agents cur-
rently in use such as vincristine, taxol and etoposide are
Published: 10 June 2009
Journal of Hematology & Oncology 2009, 2:25 doi:10.1186/1756-8722-2-25
Received: 30 December 2008
Accepted: 10 June 2009
This article is available from:
© 2009 Chan et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Journal of Hematology & Oncology 2009, 2:25
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originally purified from herbs. On the other hand, herbs
with immunomodulatory functions have mainly been
advocated by commercial sectors and most of them can be
directly purchased over the counter or the internet. Unfor-
tunately, organized efforts to investigate the actual useful-
ness of this group of herbs as well as their active
ingredients are lacking. In recent years, one of the active
ingredients responsible for the immunomodulation of
many of these herbs was found to be a form of complex
polysaccharides known as "β-D-glucan", or simply called
β-glucan [8,13]. The receptors and mechanisms of action
of β-glucans have recently been unfolded via in vitro and
in vivo animal experiments. Since β-glucans are inexpen-
sive and have good margin of safety based on historical
track records, their potential therapeutic value deserve fur-
ther investigation. We reviewed here the literature and our
experience on the in vitro and in vivo animal biological
studies of β-glucans, particularly on their immune and
anti-cancer mechanisms.
Physical and chemical properties of
β-glucans are one of the most abundant forms of polysac-
charides found inside the cell wall of bacteria and fungus.
All β-glucans are glucose polymers linked together by a
1 3 linear β-glycosidic chain core and they differ from
each other by their length and branching structures [14]
(Figure 1). The branches derived from the glycosidic chain
core are highly variable and the 2 main groups of branch-
ing are 14 or 16 glycosidic chains. These branching
assignments appear to be species specific, for example, β-
glucans of fungus have 16 side branches whereas those
of bacteria have 14 side branches. The alignments of
branching follow a particular ratio and branches can arise
from branches (secondary branches). In aqueous solu-
tion, β-glucans undergo conformational change into tri-
ple helix, single helix or random coils. The immune
functions of β-glucans are apparently dependent on their
conformational complexity [15]. It has been suggested
that higher degree of structural complexity is associated
with more potent immunmodulatory and anti-cancer
For research purposes, the composition or structural
information of β-glucans can be evaluated by a variety of
methods including liquid chromatography/mass spec-
trometry (LC/MS)[16], high performance liquid chroma-
tography (HPLC)[17] and less often X-ray crystallography
[18] or atomic force microscopy [19]. However, due to the
tedious and lack of quantitative nature of most of these
technical methods, they cannot be applied routinely as a
screening tool. Other less sophisticated techniques in
studying the β-glucans contents include phenol-sulphuric
acid carbohydrate assay, aniline blue staining method and
ELISA. Because chemical modification invariably induces
changes in the natural conformation, most of these meth-
ods cannot reflect the genuine relationship between the
structure and the bioactivity. Among them, aniline blue
staining method is a relatively simple method to screen
for β-glucan because of its ability to retain the natural con-
formation of β-glucans during the staining process. It also
has a good specificity for β-glucans but its limitation is
that it can only measure the core 13 linear glycosidic
chain and not the branches.
Endotoxin contamination is another important issue
affecting the safety and potential biological effect of β-glu-
can. Lipopolysaccharide (LPS) is an endotoxin found
inside the Gram negative bacterial cell wall and consists of
three main parts including lipid A, core and polysaccha-
ride chain [20]. Among them, lipid A was found to be the
major component that can initiate an immune response.
LPS contamination can occur during the culture or prepa-
ration of β-glucans. Since LPS is one of the most potent
immune stimulator and its contamination can lead to
false positive results in immune tests, quantification of
LPS should be performed, which can be evaluated by
either the rabbit pyrogen test or the modified limulus
amebocyte lysate (LAL) assay with devoid factor G [21].
Pharmacodynamics & Pharmacokinetics of
Most β-glucans are considered as non-digestible carbohy-
drates and are fermented to various degrees by the intesti-
nal microbial flora [22-24]. Therefore, it has been
speculated that their immunomodulatory properties may
be partly attributed to a microbial dependent effect. How-
ever, β-glucans in fact can directly bind to specific recep-
tors of immune cells, suggesting a microbial independent
immunomodulatory effect [25]. The pharmacodynamics
and pharmacokinetics of β-glucans have been studied in
animal and human models.
Animal Studies
Study using a suckling rat model for evaluation of the
absorption and tissues distribution of enterally adminis-
tered radioactive labeled β-glucan, it was found that the
majority of β-glucan was detected in the stomach and
duodenum 5 minutes after the administration [26]. This
amount rapidly decreased during first 30 minutes. A sig-
nificant amount of β-glucan entered the proximal intes-
tine shortly after ingestion. Its transit through the
proximal intestine decreased with time with a simultane-
ous increase in the ileum. Despite low systemic blood lev-
els (less than 0.5%), significant systemic
immunomodulating effects in terms of humoral and cel-
lular immune responses were demonstrated.
The pharmacokinetics following intravenous administra-
tion of 3 different highly purified and previously charac-
terized β-glucans were studied using carbohydrates
covalently labeled with a fluorophore on the reducing ter-
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minus. The variations in molecular size, branching fre-
quency and solution conformation were shown to have
an impact on the elimination half-life, volume of distribu-
tion and clearance [27].
The low systemic blood level of β-glucans after ingestion
does not reflect the full picture of the pharmacodynamics
of β-glucans and does not rule out its in vivo effects. Che-
ung-VKN et al. labeled β-glucans with fluorescein to track
their oral uptake and processing in vivo. The orally admin-
istered β-glucans were taken up by macrophages via the
Dectin-1 receptor and was subsequently transported to
the spleen, lymph nodes, and bone marrow. Within the
bone marrow, the macrophages degraded the large β-1,3-
glucans into smaller soluble β-1,3-glucan fragments.
These fragments were subsequently taken up via the com-
β-glucan is one of the key components of the fungal cell wallFigure 1
β-glucan is one of the key components of the fungal cell wall. The basic subunit of the fungal β-glucan is β-D-glucose
linked to one another by 13 glycosidic chain with 16 glycosidic branches. The length and branches of the β-glucan from
various fungi are widely different.
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plement receptor 3 (CR3) of marginated granulocytes.
These granulocytes with CR3-bound β-glucan-fluorescein
were shown to kill inactivated complement 3b (iC3b)-
opsonized tumor cells after they were recruited to a site of
complement activation such as tumor cells coated with
monoclonal antibody [28] (Figure 2). It was also shown
that intravenous administered soluble β-glucans can be
delivered directly to the CR3 on circulating granulocytes.
Furthermore, Rice PJ et al. showed that soluble β-glucans
such as laminarin and scleroglucan can be directly bound
and internalized by intestinal epithelial cells and gut asso-
ciated lymphoid tissue (GALT) cells [29]. Unlike macro-
phage, the internalization of soluble β-glucan by
intestinal epithelial cells is not Dectin-1 dependent. How-
ever, the Dectin-1 and TLR-2 are accountable for uptake of
soluble β-glucan by GALT cells. Another significant find-
ing of this study is that the absorbed β-glucans can
increase the resistance of mice to bacterial infection chal-
Human Studies
How β-glucans mediate their effects after ingestion in
human remained to be defined. In a phase I study for the
assessment of safety and tolerability of a soluble form oral
β-glucans [30]. β-glucans of different doses (100 mg/day,
200 mg/day or 400 mg/day) were given respectively for 4
consecutive days. No drug-related adverse events were
observed. Repeated measurements of β-glucans in serum,
however, revealed no systemic absorption of the agent fol-
lowing the oral administration. Nonetheless, the immu-
noglobulin A concentration in saliva increased
significantly for the 400 mg/day arm, suggesting a sys-
temic immune effect has been elicited. One limitation of
this study is the low sensitivity of serum β-glucans deter-
In summary, based on mostly animal data, β-glucans
enter the proximal small intestine rapidly and are cap-
tured by the macrophages after oral administration. The β-
glucans are then internalized and fragmented into smaller
sized β-glucans and are carried to the marrow and
endothelial reticular system. The small β-glucans frag-
ments are then released by the macrophages and taken up
by the circulating granulocytes, monocytes and dendritic
cells. The immune response will then be elicited. How-
ever, we should interpret this information with caution as
most of the proposed mechanisms are based on in vitro
The uptake and subsequent actions of β-glucan on immune cellsFigure 2
The uptake and subsequent actions of β-glucan on immune cells. β-glucans are captured by the macrophages via the
Dectin-1 receptor with or without TLR-2/6. The large β-glucan molecules are then internalized and fragmented into smaller
sized β-glucan fragments within the macrophages. They are carried to the marrow and endothelial reticular system and subse-
quently released. These small β-glucan fragments are eventually taken up by the circulating granulocytes, monocytes or macro-
phages via the complement receptor (CR)-3. The immune response will then be turned on, one of the actions is the
phagocytosis of the monoclonal antibody tagged tumor cells.
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and in vivo animal studies. Indeed, there is little to no evi-
dence for these hypothesized mechanisms of action and
pharmacokinetics occurred in human subjects at the
-glucans as immunomodulating agent
Current data suggests that β-glucans are potent immu-
nomodulators with effects on both innate and adaptive
immunity. The ability of the innate immune system to
quickly recognize and respond to an invading pathogen is
essential for controlling infection. Dectin-1, which is a
type II transmembrane protein receptor that binds β-1,3
and β-1,6 glucans, can initiate and regulate the innate
immune response [31-33]. It recognizes β-glucans found
in the bacterial or fungal cell wall with the advantage that
β-glucans are absent in human cells. It then triggers effec-
tive immune responses including phagocytosis and proin-
flammatory factors production, leading to the elimination
of infectious agents [34,35]. Dectin-1 is expressed on cells
responsible for innate immune response and has been
found in macrophages, neutrophils, and dendritic cells
[36]. The Dectin-1 cytoplasmic tail contains an immu-
noreceptor tyrosine based activation motif (ITAM) that
signals through the tyrosine kinase in collaboration with
Toll-like receptors 2 and 6 (TLR-2/6) [34,37,38]. The
entire signaling pathway downstream to dectin-1 activa-
tion has not yet been fully mapped out but several signal-
ing molecules have been reported to be involved. They are
NF-κB (through Syk-mediate pathway), signaling adaptor
protein CARD9 and nuclear factor of activated T cells
(NFAT) [39-41] (Fig. 3). This will eventually lead to the
release of cytokines including interleukin (IL)-12, IL-6,
tumor necrosis factor (TNF)-α, and IL-10. Some of these
cytokines may play important role in the cancer therapy.
On the other hand, the dendritic cell-specific ICAM-3-
grabbing non-integrin homolog, SIGN-related 1
(SIGNR1) is another major mannose receptor on macro-
phages that cooperates with the Dectin-1 in non-opsonic
recognition of β-glucans for phagocytosis [42] (Fig 3).
Furthermore, it was found that blocking of TLR-4 can
inhibit the production of IL-12 p40 and IL-10 induced by
purified Ganoderma glucans (PS-G), suggesting a vital
role of TLR-4 signaling in glucan induced dendritic cells
maturation. Such effect is also operated via the augmenta-
tion of the IκB kinase, NF-κB activity and MAPK phospho-
rylation [43]. One additional point to note is that those
studies implied the interaction between β-glucans and
TLR all used non-purified β-glucans, therefore the actual
involvement of pure β-glucans and TLR remains to be
Other possible receptors and signaling pathways induced
by β-glucans are less definite at the moment. For example,
lentinan, a form of mushroom derived β-glucans, has
been found to bind to scavenger receptor found on the
surface of myeloid cells and triggers phosphatidylinositol-
3 kinase (PI3K), Akt kinase and p38 mitogen-activated
protein kinase (MAPK) signaling pathway [44](Fig. 3).
But no specific β-glucans scavenger receptor has been
identified so far. Candida albicans derived β-glucans but
not other forms of pathogenic fungal β-glucans can bind
to LacCer receptor and activate the PI-3K pathway in con-
trolling the neutrophil migration [45] (Fig. 3), but such
activation pathway may involve other molecules found in
the Candida derived β-glucans.
We found that β-glucans can induce human peripheral
blood mononuclear cells proliferation [46]. It can also
enhance phenotypic and functional maturation of mono-
cyte derived dendritic cells with significant IL-12 and IL-
10 production. Similar findings were found by Lin et al.
using PS-G, in addition, treatment of dendritic cells with
PS-G resulted in enhanced T cell-stimulatory capacity and
increased T cell secretion of interferon-γ and IL-10
[43,47]. This action is at least mediated in part through
the Dectin-1 receptor. The potency of such immunomod-
ulating effects differs among β-glucans and purified
polysaccharides of different size and branching complex-
ity. In general, bigger size and more complex β-glucans
such as those derived from Ganoderma lucidum have
higher immunomodulating potency.
The adaptive immune system functions through the com-
bined action of antigen-presenting cells and T cells. Spe-
cifically, class I major histocompatibility complex (MHC-
I) antigen presentation to CD8(+) cytotoxic T cells is lim-
ited to proteosome-generated peptides from intracellular
pathogens. On the other hand, the class II MHC (MHC-II)
endocytic pathway presents only proteolytic peptides
from extracellular pathogens to CD4(+) T helper cells.
Carbohydrates have been previously thought to stimulate
immune responses independently of T cells [48]. How-
ever, zwitterionic polysaccharides (polysaccharides that
carry both positive and negative charges) such as β-glu-
cans can activate CD4(+) T cells through the MHC-II
endocytic pathway [49]. β-glucans are processed to low
molecular weight carbohydrates by a nitric oxide-medi-
ated mechanism. These carbohydrates will then bind to
MHC-II inside antigen-presenting cells such as dendritic
cells for presentation to T helper cells. Initial data sug-
gested that it subsequently leads to Th-1 response, but
there are conflicting data related to this aspect. In our in
vitro data, β-glucans do not tend to polarize T cells into
either Th-1, Th-2 or regulatory T cells [46]. However,
recent publications suggested β-glucans such as zymosan
may induce T-cells into T-reg cells in a NOD mice model
[50]. Therefore, whether β-glucans can induce important
immunologic responses through T cell activation remain
to be further investigated.
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Immune activation induced by β-glucansFigure 3
Immune activation induced by β-glucans. β-glucans can act on a variety of membrane receptors found on the immune
cells. It may act singly or in combine with other ligands. Various signaling pathway are activated and their respective simplified
downstream signaling molecules are shown. The reactors cells include monocytes, macrophages, dendritic cells, natural killer
cells and neutrophils. Their corresponding surface receptors are listed. The immunomodulatory functions induced by β-glucans
involve both innate and adaptive immune response. β-glucans also enhance opsonic and non-opsonic phagocytosis and trigger a
cascade of cytokines release, such as tumor necrosis factor(TNF)-α and various types of interleukins (ILs).
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Another mechanism of β-glucan action is mediated via
the activated complement receptor 3 (CR3, also known as
CD11b/CD18), which is found on natural killer (NK)
cells, neutrophils, and lymphocytes. This pathway is
responsible for opsonic recognition of β-glucans leading
to phagocytosis and reactor cells lysis. β-glucans bind to
the lectin domain of CR3 and prime it for binding to inac-
tivated complement 3b (iC3b) on the surface of reactor
cells. The reactor cells can be of any cell type including
cancer cells tagged with monoclonal antibody and coated
with iC3b. The β-glucans-activated circulating cells such
as the CR3 containing neutrophils will then trigger cell
lysis on iC3b-coated tumor cells [28]. Similarly, majority
of the human NK cells express CR3 and it was shown that
opsonization of NK cells coated with iC3b leads to an
increase in the lysis of the target. The beta chain of the
CR3 molecule (CD18) rather than the alpha chain
(CD11b) is responsible to the β-glucan binding [51,52].
This concept was supported by in vivo study demonstrat-
ing barley β-1,3;1,4-glucan given orally can potentiate the
activity of an antitumor monoclonal antibody (anti-gan-
glioside-2 or "3F8"), leading to enhanced tumor regres-
sion and survival on a human neuroblastoma xenografts
mouse model [53]. 3F8 plus β-glucan was shown to pro-
duce near-complete tumor regression or disease stabiliza-
tion whereas 3F8 or β-glucan alone showed no significant
effect. The median survival of the 3F8 plus β-glucan group
was 5.5-fold higher than that of the control groups, and
up to 47% of the mice remained progression free in con-
trast to <3% of controls at the end of the study period. No
toxicities were noted in all mice treated with β-glucan,
3F8, or 3F8 plus β-glucan.
A similar xenograft model was adopted subsequently for
investigating various targeted tumor antigens and tumor
types. It was found that β-glucan exerts similar anti-tumor
effects irrespective of antigens (GD2, GD3, CD20, epider-
mal growth factor-receptor, and HER-2) or human tumor
types (neuroblastoma, melanoma, lymphoma, epider-
moid carcinoma, and breast carcinoma) or tumor sites
(subcutaneous versus systemic). The effect was correlated
with the molecular size of the β-1,3;1,4-glucan [53,54].
Furthermore, 2 other receptors known as scavenger [55]
and lactosylceramide [56,57] also bind β-glucans and can
elicit a range of responses. β-glucans can enhance endo-
toxin clearance via scavenger receptors by decreasing TNF
production leading to improved survival in rats subjected
to Escherichia coli sepsis [58]. On the other hand, β-glu-
cans binding to lactosylceramide receptor can enhance
myeloid progenitor proliferation and neutrophil oxida-
tive burst response, leading to an increase in leukocyte
anti-microbial activity. It is also associated with the activa-
tion of NF-κB in human neutrophils [59]. Again in other
studies, structurally different β-glucans appear to have dif-
ferent affinity toward these receptors. For example, only
high molecular weight β-glucans can effectively bind to
the lactosylceramide receptor. Therefore, markedly differ-
ent host responses induced by different β-glucans are
In summary, β-glucans act on a diversity of immune
related receptors in particularly Dectin-1 and CR3, and
can trigger a wide spectrum of immune responses. The tar-
geted immune cells of β-glucans include macrophages,
neutrophils, monocytes, NK cells and dendritic cells (Fig-
ure 3). The immunomodulatory functions induced by β-
glucans involve both innate and adaptive immune
response. β-glucans also enhance opsonic and non-
opsonic phagocytosis. Whether β-glucans polarize the T
cells subset towards a particular direction remains to be
Anti-cancer effects of
It is becoming clear that β-glucans themselves have no
direct cytotoxic effects. Studies implicating the cytotoxic
effects of β-glucans were either from studies using crude
extracts of β-glucan containing herbs or the use of β-glu-
can primed monocytes. For β-glucan containing herbs like
Ganoderma lucidum (Lingzhi), there are other active com-
ponents such as ganoderic acid from its mycelium [60]
and triterpenes from its spore [61-63], which have all
been shown to have direct anti-cancer effects independ-
ently. We did not find any direct cytotoxic effects of β-glu-
cans on a panel of common cancer cell lines tested
including carcinoma, sarcoma, and blastoma. β-glucans
also did not trigger any apoptotic pathways and had no
direct effect on the telomerase and telomeric length of the
cancer cells (unpublished data). In contrast, it stimulated
the proliferation of monocytic lineage leukemic cells in-
vitro and can facilitate the maturation of dendritic cells
derived from leukaemic cells [64]. Hence, whether it is
beneficial to apply β-glucans on leukemic patients
remains controversial and has to be considered with cau-
In the English literature, there are no clinical trials that
directly assessed the anti-cancer effects of purified β-glu-
cans in cancer patients. Most studies were assessing the
toxicity profile or underlying immune changes of the can-
cer patients without addressing on the change of cancer
status. In addition, most of the related studies used either
crude herbal extracts or a fraction of the extracts instead of
purified β-glucans. Therefore, it is difficult to identify
whether the actual effects were related to β-glucans or
other confounding chemicals found in the mixture.
In a prospective clinical trial of short term immune effects
of oral β-glucan in patients with advanced breast cancer,
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23 female patients with advanced breast cancer were com-
pared with 16 healthy females control [65]. Oral β-
1,3;1,6-glucan was taken daily. Blood samples were recol-
lected on the day 0 and 15. It was found that despite a rel-
atively low initial white cell count, oral β-glucan can
stimulate proliferation and activation of peripheral blood
monocytes in patients with advanced breast cancer.
Whether that can be translated into clinical benefit
remains unanswered.
Clinical trials on anti-cancer effects of natural products
Many edible fungi particularly in the mushroom species
yield immunogenic substances with potential anticancer
activity [66]. β-glucans are one of the common active
components (Table 1). In limited clinical trials on human
cancers, most were well tolerated. Among them, lentinan
derived from Lentinus edodes is a form of β-glucans [67].
Since it has poor enteric absorption, intrapleural, intra-
peritoneal [68] or intravenous routes had been adopted in
clinical trials which showed some clinical benefit when
used as an adjuvant to chemotherapy [69]. Schizophyllan
(SPG) or sizofiran is another β-glucan derived from Schiz-
ophyllan commune. Its triple helical complex β-glucans
structure prevents it from adequate oral absorption so an
intratumoral route or injection to regional lymph nodes
had been adopted [70,71]. In a randomized trial, SPG
combined with conventional chemotherapy improved
the long term survival rate of patients with ovarian cancer
[72]. But whether the prolonged survival can subse-
quently led to a better cure rate remain unanswered.
Maitake D-Fraction extracted from Grifola frondosa
(Maitake mushroom) was found to decrease the size of
the lung, liver and breast tumors in >60% of patients
when it was combined with chemotherapy in a 2 arms
control study comparing with chemotherapy alone [73].
The effects were less obvious with leukemia, stomach and
brain cancer patients [74]. But the validity of the clinical
study was subsequently questioned by another independ-
ent observer [75]. Two proteoglycans from Coriolus versi-
color (Yun Zhi) – PSK (Polysaccharide-K) and PSP
(Polysaccharopeptide) – are among the most extensively
studied β-glucan containing herbs with clinical trials
information. However, both PSK and PSP are protein-
bound polysaccharides, so their actions are not necessary
directly equivalent to pure β-glucans [76]. In a series of tri-
als from Japan and China, PSK and PSP were well toler-
ated without significant side effects [66,77-81]. They also
prolonged the survival of some patients with carcinoma
and non-lymphoid leukemia.
Ganoderma polysaccharides are β-glucans derived from
Ganoderma lucidum (Lingzhi, Reishi). While β-glucan is
the major component of the Ganoderma mycelium, it is
only a minor component in the Ganoderma spore [7].
The main active ingredient in the Ganoderma spore extract
is triterpenoid which is cytotoxic in nature. In an open-
label study on patients with advanced lung cancer, thirty-
six patients were treated with 5.4 g/day Ganoderma
polysaccharides for 12 weeks with inconclusive variable
and results on the cytokines profiles [82]. Another study
on 47 patients with advanced colorectal cancer using the
Table 1: Selected Medicinal Mushroom with β-glucans as Active Components
Herbs Common Name β-glucans structure Types of β-glucans
Lentinus edodes Shiitake mushroom β-1,3;1,6-glucan Lentinan
Schizophyllan commune Brazilian mushroom, Schizophyllan β-1,3;1,6-glucan Schizophyllan (SPG) or sizofiran
Grifola frondosa Maitake mushroom β-1,3;1,6-glucan with xylose and
Maitake D-Fraction
Coriolus versicolor Yun Zhi Protein bound β-1,3;1,6-glucan PSP (polysaccharide peptide) PSK
(polysaccharide-Kureha or polysaccharide-K,
Ganoderma lucidum Lingzhi, Reishi β-1,3;1,6-glucan Ganoderma polysaccharides, Ganopoly
Agaricus blazei Brazilian sun-mushroom,
Himematsutake mushroom
Protein bound β-1,6-glucan Agaricus polysaccharides
Pleurotus ostreatus Oyster mushroom, píng gû β-1,3-glucan with galactose and
Coprinus comatus Shaggy ink cap, lawyer's wig, or
shaggy mane
β-1,3-glucan Coprinus polysaccharides
Journal of Hematology & Oncology 2009, 2:25
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same dosage and period again demonstrated similar vari-
able immune response patterns [83]. These results high-
light the inconsistency of clinical outcomes in using
immune enhancing herbal extracts clinically, which may
partly be due to the impurity of the products used.
The intrinsic differences of the β-glucans derived from dif-
ferent sources will elicit variable immune and anti-cancer
responses. We summarized the current limitations of β-
glucan research from the literature (Table 2). The limita-
tions are further complicated by the fact that many studies
on β-glucan related herbs often used crude extracts rather
than purified compounds, therefore the confounding
effects of other chemicals cannot be totally ruled out [84].
Careful selection of appropriate β-glucan products with
good pre-test quality control is essential if we want to
understand and compare the results on how β-glucans act
on our immune system and exerting anti-cancer effects. A
possibly well-defined β-glucan standard is urgently
needed in this field for controlled experiments. So far,
there are very few clinical trial data on using purified β-
glucans for cancer patients. Future studies should aim to
obtain such information so it can assist us in applying β-
glucans rationally and effectively to our cancer patients in
the future.
Competing interests
The authors declare that there is no conflict of interests,
including conflicts of financial nature involving any phar-
maceutical or commercial company.
Authors' contributions
GCFC initiated the concept, wrote and revised the manu-
script and creating the illustrations. WKC involved in writ-
ing, coordination and revising the manuscript. DMS
involved in the preparation and revision of manuscript.
We would like to thank Dr. Anita Chan (U. Alberta) for the English editing,
Mr. Spencer Ng for the production of the graphic figures, the Edward Sai-
Kim Hotung Paediatric Education & Research Fund, URC/CRCG Grants
and Pau Kwong Wun Charitable Foundation for supporting the beta-glucan
related works.
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... The cell walls of S. cerevisiae cells account for 30% of their dry weight and are composed of β-glucan, mannan, protein, lipid, and chitin [3,4]. β-glucan is one of the most common polysaccharides found in the cell walls of bacteria, yeast, and fungi [5]. It is composed of a β(1 → 3)glucan backbone with a β(1 → 6)-glucan side chain [4]. ...
... β-Glucan and mannoprotein compose the majority of yeast cell wall components [40]. β-glucan, a glucose polymer linked by 1 → 3 linear glycosidic bonds, has various lengths and branching structures [5]. Mannoprotein stimulates angiogenesis in endothelial cells via the Erk/ Akt/eNOS signaling pathway [11]. ...
... Mannoprotein stimulates angiogenesis in endothelial cells via the Erk/ Akt/eNOS signaling pathway [11]. The structural complexity of β-glucan determines its functionality [5]. β-glucan has a variety of biological activities, including alleviation of cardiovascular disease, dyslipidemia, and obesity [10]. ...
The role of yeast-derived β-glucan in angiogenesis has not been elucidated because there have been few specific studies on its clinical and physiological significance. Therefore, this study investigated the correlation between β-glucan and histone deacetylase 5 (HDAC5) in human umbilical vein endothelial cells (HUVECs), revealing the role of β-glucan in angiogenesis. We confirmed that HDAC5 was phosphorylated by β-glucan stimulation and released from the nucleus to the cytoplasm. Furthermore, we found that β-glucan-stimulated HDAC5 translocation mediates the transcriptional activation of MEF2. As a result, the expression of KLF2, EGR2, and NR4A2, whose expression is MEF2-dependent and involved in angiogenesis, increased. Thus, we showed the activity of β-glucan in angiogenesis through in vitro and ex vivo assays including cell migration, tube formation, and aortic ring analyses. Specifically, application of an HDAC5 inhibitor repressed MEF2 transcriptional activation in both in vitro and ex vivo angiogenesis. HDAC5 inhibitor LMK235 inhibited the proangiogenic activity of beta-glucan, suggesting that β-glucan induces angiogenesis through HDAC5. These findings suggest that HDAC5 is essential for angiogenesis, and that β-glucan induces angiogenesis. In conclusion, this study demonstrates that β-glucan induces angiogenesis through HDAC5. It also suggests that β-glucan has potential value as a novel therapeutic agent for modulating angiogenesis.
... Indeed, monocytes are important immune cells that recognize pathogen molecules in several inflammatory diseases in either sepsis (Aguilar-Briseño et al., 2020) or non-sepsis (Grip et al., 2007;Mukherjee et al., 2015;Weldon et al., 2015). Although both LPS and BG can stimulate monocytes (Chan et al., 2009;Kew et al., 2017), the simultaneous presence of LPS with BG synergistically activates inflammation (Issara-Amphorn et al., 2018) which might be similar to the condition of dengue-induced leaky gut. On the other hand, the chronic presence of LPS might induce endotoxin tolerance, a reduced LPS responses after the first dose of LPS (Ondee et al., 2019), partly through the interference of cellular energy status (Gillen et al., 2021), which might be associated with ineffective organismal control after viral infection (post-dengue secondary bacterial infection) (Sharma, 2020). ...
Full-text available
Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-β-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14-CD16+) and NK cells (CD56+CD16-) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection.
... Lentinan (LNT), which is a purified β-1,3-glucan with β-1,6-branches isolated from Lentinus edodes. LNT, which is known for its immune activity like other β-glucans from medicinal mushrooms (1)(2)(3), has been reported as an intravenous antitumor polysaccharide via enhancement of the host immune system (4). The clinical efficacy of LNT, such as its effect on long-term survival and improvement of life quality, has been confirmed in cancer patients (5,6). ...
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The β-Glucans widely exist in plants and edible fungi, and their diverse bioactivities and good physicochemical properties have been widely reported. In addition, β-glucan intravenous injections (such as lentinan and schizophyllan) have been clinically used as immunomodulators and antitumor polysaccharides. However, the pharmacokinetic studies of β-glucans only stay on the level of plasma concentration and biodistribution in vivo , and little is known about their metabolism and degradation in vivo , which severely limits the further application of β-glucans in the field of medicine and biomaterials. The aim of this paper is to explore the metabolism and degradation process of lentinan (as a representative of β-glucans) in vivo by labeling it with water-soluble fluorescein 5-([4, 6-Dichlorotriazin-2-yl]amino)fluorescein (DTAF). Fluorescently labeled lentinan (FLNT) was intravenously administered to rats at a single dose of 8 mg/kg. The degradation of LNT in blood, liver, kidney, and urine was evaluated by the gel permeation chromatography. Our results showed that although LNT could be degraded in blood, liver, kidney, and urine, there were still some prototypes until excreted in urine due to the incomplete degradation of LNT in each step. To the best of our knowledge, this is the first report to comprehensively study LNT metabolic degradation in rats. These results provide an important reference for further exploration and application of LNT and other β-glucans.
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Therapeutic tumor neoantigen vaccines have been widely studied given their good safety profile and ability to avoid central thymic tolerance. However, targeting antigen‐presenting cells (APCs) and inducing robust neoantigen‐specific cellular immunity remain challenges. Here, a safe and broad‐spectrum neoantigen vaccine delivery system is proposed (GP‐Neoantigen) based on β‐1,3‐glucan particles (GPs) derived from Saccharomyces cerevisiae and coupling peptide antigens with GPs through convenient click chemistry. The prepared system has a highly uniform particle size and high APC targeting specificity. In mice, the vaccine system induced a robust specific CD8+ T cell immune response and humoral immune response against various conjugated peptide antigens and showed strong tumor growth inhibitory activity in EG7·OVA lymphoma, B16F10 melanoma, 4T1 breast cancer, and CT26 colon cancer models. The combination of the toll‐like receptors (TLRs) agonist PolyI:C and CpG 2395 further enhanced the antitumor response of the particle system, achieving complete tumor clearance in multiple mouse models and inducing long‐term rejection of reinoculated tumors. These results provide the broad possibility for its further clinical promotion and personalized vaccine treatment. A broad‐spectrum neoantigen vaccine delivery system (GP‐Neoantigen) based on β‐1,3‐glucan particles (GPs) derived from Saccharomyces cerevisiae induces a robust cellular and humoral immune response against conjugated peptide antigens and strongly inhibits tumor growth, with which complete tumor clearance and long‐term rejection of reinoculated tumors can be achieved in multiple mouse tumor models.
Introduction Herbal medicine is extensively used in various therapeutic strategies. Althaea officinalis L. of the family Malvaceae exhibits many biological activities through its phenolic acids, flavonoids, coumarins and polysaccharides. In Lebanon, the flowers are consumed in hot infusions. Therefore, the current study aimed to evaluate chemical and biological properties of Lebanese Althaea officinalis L. flower water extract. Methods Chemical characterization was performed by qualitative phytochemical screening, gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC-MS). Anti-proliferative effect was evaluated in cancer cells by MTT assay. The mRNA expression levels of pro-inflammatory enzyme and inflammatory cytokines were assessed in LPS-stimulated RAW 264.7 cells. Cytoprotective activity was examined in red blood cells against hydrogen peroxide-induced hemolysis. Antioxidant property was assessed by DPPH radical scavenging assay. Results Qualitative phytochemical screening of the extract revealed the presence of anthraquinones, flavonoids, lignins, phenols, tannins, terpenoids and others. GC/MS analysis suggested that most of the phytocompounds are conjugated to sugars rather than free. LC/MS analysis identified 5 phenolic acids (syringic, gallic, caffeic, p-coumaric and trans-ferulic acids) and 8 flavonoids (catechin, apigenin, chrysin, quercetin, kaempferol, genistein, rutin trihydrate and galangin). Biological evaluation of the extract showed anti-proliferative effects on A549, EB, HCT-116, MCF-7 and HeLa 229 cells, anti-inflammatory activity illustrated by decrease in mRNA expression of inducible nitric oxide synthase, interleukin 1 beta, tumor necrosis factor alpha and interleukin 6, cytoprotective activity in red blood cells and antioxidant property. Conclusion Althaea officinalis flowers rich in phytocompounds exert interesting biological activities and hold promise in the pharmacological field.
The field of psychoneuroimmunology has made significant advances in understanding mechanisms underlying signaling between the immune system and central nervous system since the initial coinage of the term in 1975 and especially in the past 25 years. The current review explores the research supporting the premise that the immune system impacts behavior, including risk of developing stress-related psychiatric disorders (e.g., anxiety disorders, affective disorders, and trauma- and stressor-related disorders such as posttraumatic stress disorder). Beginning with the recent call to examination of interoception as a mental health-relevant signal, inflammation is explored as an important interoceptive signal. Inflammation is viewed through the lens of sickness behavior, before broadening to include the impact of the immune system on a collection of mental-health-related symptoms. This is explored mechanistically through the direct effects of cytokine signaling on the brain, the impact of afferent vagus nerve signaling, and through examination of the role of bone-marrow-derived monocytes in relaying peripheral immune signals to the brain. Immature bone-marrow-derived monocytes contribute to increased peripheral inflammation, but also have the capacity to traffic to brain regions relevant to stress-related psychiatric disorders. This trafficking can increase neuroinflammation causing anxiety-like defensive behavioral responses in mouse models and has been linked to symptoms of stress-related psychiatric disorders in humans. Additionally, the commensal bacteria inhabiting the gut (gut microbiota) exert a modulating effect on inflammation and behavior through several mechanisms, including signaling in the systemic circulation, shifting the body's stress dynamics, and altering inflammatory balance in the gut and the rest of the body. These mechanisms are discussed in the context of mental health conditions, including mood disorders, anxiety disorders, and trauma- and stressor-related disorders. There is a preponderance of evidence supporting the fact that peripheral immune activity and neuroinflammation impact behavior and mental health. Further research will continue to elucidate the mechanisms involved.
Background Duchenne muscular dystrophy is a hereditary muscular disease involving degeneration (i.e. atrophy and loss of muscle fibres) of skeletal muscles, including the diaphragm, and progressively severe functional decline. A previous study shows Polycan, a type of β-glucan derived from the black yeast Aureobasidium pullulans (SM-2001), promotes osteogenicity and bone loss, and possesses anti-inflammatory activity to induce inflammatory cytokines in human immune and cancer cells. Objective In this study, we evaluated changes in exercise load behaviour measurements and changes in muscle-related physiological indicators following oral administration of Polycan in mdx mice, an experimental animal model of Duchenne muscular dystrophy. Result In mdx mice, Polycan prevented weight loss and thickness of skeletal muscle. In addition, by monitoring increases in running time of mice on treadmills and performing a grip strength test, we confirmed reduced muscle function was recovered to some extent after administering Polycan to mdx mice. In addition, we confirmed that Polycan significantly altered mRNA expression in a concentration-dependent manner, whereby myogenic transcription factors (MyoD, Myf5 and Myogenin) increased and FoxO3α, MuRF1 and Atrogin-1 decreased. We aimed to investigate the mechanism of action in Polycan on energy metabolism of p-AMPK, SIRT1 and PGC1α with apoptosis expression levels as factors related to signalling pathways. Expression ratios of cleaved-caspase-3/caspase-3 and Bax/Bcl-2 in the Polycan extract-administered group increased compared with the control group. Conclusion These results demonstrate that Polycan can improve and protect muscle atrophy by preventing apoptosis via pathway regulation related to myogenic transcription factors and energy metabolism in mdx mice.
Acute graft‐versus‐host disease (aGvHD) remains a major threat to a successful outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Although antibody‐based targeting of the CD40/CD40 ligand costimulatory pathway can prevent aGvHD, side effects hampered their clinical application, prompting a need for other ways to interfere with this important dendritic T‐cell costimulatory pathway. Here, we used small interfering RNA (siRNA) complexed with β‐glucan allowing the binding and uptake of the siRNA/β‐glucan complex (siCD40/schizophyllan [SPG]; chemical modifications called NJA‐312, NJA‐302, and NJA‐515) into Dectin1+ cells, which recognize this pathogen‐associated molecular pattern receptor. aGvHD was induced by the transplantation of splenocytes and bone marrow cells from C57BL/6J into CBF1 mice. Splenic dendritic cells retained Dectin1 expression after HSCT but showed lower expression after irradiation. The administration of siCD40/SPG, NJA‐312, and NJA‐302 ameliorated aGvHD‐mediated lethality and tissue damage of spleen and liver, but not skin. Multiple NJA‐312high injections prevented aGvHD but resulted in early weight loss in allogeneic HSCT mice. In addition, NJA‐312 treatment caused delayed initial donor T and B‐cell recovery but resulted in stable chimerism in surviving mice. Mechanistically, NJA‐312 reduced organ damage by suppressing CCR2+, F4/80+, and IL17A‐expressing cell accumulation in spleen, liver, and thymus but not the skin of mice with aGvHD. Our work demonstrates that siRNA targeting of CD40 delivered via the PAMP‐recognizing lectin Dectin1 changes the immunological niche, suppresses organ‐specific murine aGvHD, and induces immune tolerance after organ transplantation. Our work charts future directions for therapeutic interventions to modulate tissue‐specific immune reactions using Pathogen‐associated molecular pattern (PAMP) molecules like 1,3‐β‐glucan for cell delivery of siRNA.
The immunomodulatory effects and signalling pathways of five water-soluble yeast β-glucan fractions (WYG1–5) with different molecular weights (Mw) and chain conformations were investigated in RAW264.7 macrophages. All five WYG fractions were shown to increase nitric oxide (NO) production, phagocytosis activity and cytokine secretion compared with the normal group. The incubation of cells with WYG for 2 h and then with lipopolysaccharide (LPS) for 24 h showed an inhibition of NO production, phagocytosis activity, cytokine secretion, and the expression of inducible nitric oxide synthase (iNOS) and cytokine mRNA compared with the LPS group. The results showed a two-way immunomodulatory effect of WYG on inflammatory factors, with the best effect for WYG-2 having a Mw of 2830 × 10³ g/mol and spherical conformation. Furthermore, both mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signalling pathways were triggered in the two-way immunomodulation. This study reveals the structure-activity relationship and provides a pharmacological basis for controlling inflammatory disorders with WYG.
Yeast has been employed as an effective derived drug carrier as a unicellular microorganism. Many research works have been devoted to the encapsulation of nucleic acid compounds, insoluble small molecule drugs, small molecules, liposomes, polymers, and various nanoparticles in yeast for the treatment of disease. Recombinant yeast-based vaccine carriers (WYV) have played a major role in the development of vaccines. Herein, the latest reports on the application of yeast carriers and the development of related research are summarized, a conceptual description of gastrointestinal absorption of yeast carriers, as well as the various package forms of different drug molecules and nanoparticles in yeast carriers are introduced. In addition, the advantages and development of recombinant yeast vaccine carriers for the disease, veterinary and aquaculture applications are discussed. Moreover, the current challenges and future directions of yeast carriers are proposed.
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The digestibility of polysaccharides and other major components and the metabolic response of the microflora in the small and large intestines to oat diets varying in mixed linked (β(l →3; 1 →4)-D-glucan β-glucan) were studied in experiments with ileum-cannulated pigs. The oat fractions for diets were prepared in a dry milling process in which oat groats were milled into two endosperm fractions (oat flour 1 and oat flour 2) and oat bran. The digestibility of polysaccharides and the metabolic response of the microflora were followed for the two contrasting diets, oat flour 1 and oat bran, from ingestion to excretion while the digestibility of oat groats and oat flour 2 were estimated only at the ileum and in faeces. There was no degradation of β-glucan from either oat flour 1 or bran in the stomach and the first, middle and distal thirds of the small intestine (average digestibility approximately 0), while in the terminal ileum digestibility increased to 0·30 to 0·17 respectively. The digestion of starch in the first third of the small intestine was lower for the high-β-glucan oat-bran diet (0·49) than for the low-β-glucan flour diet (0·64). However, digestibility differences between the two diets levelled out as the digesta moved aborally in the small intestine and the digestibility at the terminal ileum was almost complete (0·970–0·995) for all diets. Oat non-starch polysaccharides (NSP) were an easily digestible energy source for the microflora in the large intestine less than 13% of dietary NSP being recovered in faeces. The bulk of β-glucan which survived the small intestine was degraded in the caecum and proximal colon while arabinoxylan was more slowly degraded. The amount of residues passing the ileo-caecal junction has little impact on the density of micro-organisms in the large intestine, which on the flour and bran diets were in the range of 1010–1011 viable counts/g digesta, but a high impact on the activity of the flora in colon. Oat bran resulted in a higher proportion of butyric acid in large intestinal content compared with the flour diet. The faecal bulking effect of oat bran was mainly caused by an increased excretion of protein and fat, presumably of bacterial origin. Of all the diets tested the oat-bran diets had the lowest digestibilities of protein and fat at the terminal ileum and in the faeces.
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Previous studies demonstrated Ganoderma lucidum polysaccharides (GL-PS), a form of bioactive beta-glucan can stimulate the maturation of monocyte-derived dendritic cells (DC). The question of how leukemic cells especially in monocytic lineage respond to GL-PS stimuli remains unclear. In this study, we used in vitro culture model with leukemic monocytic cell-lines THP-1 and U937 as monocytic effectors cells for proliferation responses and DCs induction. We treated the THP-1 and U937 cells with purified GL-PS (100 microg/mL) or GL-PS with GM-CSF/IL-4. GL-PS alone induced proliferative response on both THP-1 and U937 cells but only THP-1 transformed into typical DC morphology when stimulated with GL-PS plus GM-CSF/IL-4. The transformed THP-1 DCs had significant increase expression of HLA-DR, CD40, CD80 and CD86 though not as high as the extent of normal monocyte-derived DCs. They had similar antigen-uptake ability as the normal monocyte-derived DCs positive control. However, their potency in inducing allogeneic T cell proliferation was also less than that of normal monocyte-derived DCs. Our findings suggested that GL-PS could induce selected monocytic leukemic cell differentiation into DCs with immuno-stimulatory function. The possible clinical impact of using this commonly used medicinal mushroom in patients with monocytic leukemia (AML-M4 and M5) deserved further investigation.
Since the publication of the first edition, important developments have emerged in modern mushroom biology and world mushroom production and products. The relationship of mushrooms with human welfare and the environment, medicinal properties of mushrooms, and the global marketing value of mushrooms and their products have all garnered great attention, identifying the need for an updated, authoritative reference. Mushrooms: Cultivation, Nutritional Value, Medicinal Effect, and Environmental Impact, Second Edition presents the latest cultivation and biotechnological advances that contribute to the modernization of mushroom farming and the mushroom industry. It describes the individual steps of the complex mushroom cultivation process, along with comprehensive coverage of mushroom breeding, efficient cultivation practices, nutritional value, medicinal utility, and environmental impact. Maintaining the format, organization, and focus of the previous edition, this thoroughly revised edition includes the most recent research findings and many new references. It features new chapters on medicinal mushrooms and the effects of pests and diseases on mushroom cultivation. There are also updated chapters on specific edible mushrooms, and an expanded chapter on technology and mushrooms. Rather than providing an encyclopedic review, this book emphasizes worldwide trends and developments in mushroom biology from an international perspective. It takes an interdisciplinary approach that will appeal to industrial and medical mycologists, mushroom growers, botanists, plant pathologists, and professionals and scientists in related fields. This book illustrates that mushroom cultivation has and will continue to have a positive global impact on long-term food nutrition, health care, environmental conservation and regeneration, and economic and social change.
Glucans are cell wall constituents of fungi and bacteria that bind to pattern recognition receptors and modulate innate immunity, in part, by macrophage activation. We used surface plasmon resonance to examine the binding of glucans, differing in fine structure and charge density, to scavenger receptors on membranes isolated from human monocyte U937 cells. Experiments were performed at 25degreesC using a biosensor surface with immobilized acetylated low density lipoprotein (AcLDL). Inhibition of the binding by polyinosinic acid, but not polycytidylic acid, confirmed the interaction of scavenger receptors. Competition studies showed that there are at least two AcLDL binding sites on human U937 cells. Glucan phosphate interacts with all sites, and the CM-glucans and laminarin interact with a subset of sites. Polymer charge has a dramatic effect on the affinity of glucans with macrophage scavenger receptors. However, it is also clear that human monocyte scavenger receptors recognize the basic glucan structure independent of charge.
Cells responsible for the natural killer (NK) effect in the human blood can be collected in the low-density lymphocyte subset and the majority of them express CR3. In addition to the iC3b binding site the CR3 molecules possess an epitope which binds beta-glucan. Ligands of this site can deliver activation signals to CR3-carrying monocytes and neutrophils. We found that the function of NK cells was also potentiated by preincubation with beta-glucan. The treatment increased the proportion of target-binding lymphocytes and of the damaged target cells in the conjugates. The monoclonal antibody OKM-1, directed to the beta-glucan-binding site of CR3, abrogated this effect. Another CR3-reactive monoclonal antibody, M522, known to activate monocytes and neutrophils, enhanced the NK function.
In order to ascertain a correlation between infiltration of Langerhans cells (LCs) or T-cells in tumor tissues and the intratumoral administration of a biological response modifier, Sizofiran (SPG) was analyzed in cancer of the uterine cervix. Cancer specimens of 45 patients with stage II–III invasive cervical cancers were analyzed. SPG was administered to the cervical tumor at high and low concentrations (Strong SPG and weak SPG) as well as by intramuscular injection twice a week. LC and T-cell infiltrations to tumor tissues of the uterine cervix were studied immunohistochemically and electron microscopically. Of 10 patients with systemic but no local immunization, 1 (10.0%) showed an increase in LC infiltration and 2 (20.0%) showed a decrease. Of 15 patients with strong SPG immunization, 2 (13%) showed an increase and 5 (33%) showed a decrease. In contrast, of 20 patients with weak SPG immunization, the incidence of increase in LC infiltration was 55% (11 patients), significantly greater than the above-mentioned groups and none showed a decrease. Of the 20 patients with weak SPG administration, 3 (15%) showed T-cell infiltration before SPG administration, and 12 (60%) showed an increase in T-cell infiltration after SPG was given. Up on electron microscopy, Birbeck granules in the cytoplasm of LC significantly increased after SPG immunization, indicating activation of LC. In conclusion, the present study suggested that the LC and T-cell infiltrations in cancer tissues were augmented by intratumoral SPG administration at a certain concentration. Intratumoral administration of SPG may be applied to improve the prognosis after multidisciplinary treatment of advanced cervical cancer.
(1→3)-β-d-Glucans that have β-d-glucopyranosyl units attached by (1→6) linkages as single unit branches enhance the immune system systemically. This enhancement results in antitumor, antibacterial, antiviral, anticoagulatory and wound healing activities. The (1→3)-β-d-glucan backbone is essential. The most active polymers have degrees of branching (DB) between 0.20 and 0.33. Data suggest both that triple helical structures formed from high molecular weight polymers are possibly important for immunopotentiating activity and that activity is independent of any specific ordered structure. Other data indicate that it is the distribution of the branch units along the backbone chain that is responsible for activity. There are data that indicate both that β-d-glucopyranosyl units are required for immunopotentiating activity and that the specific nature of the substituent is unimportant. There are also data that indicate both that the more water-soluble polymers are more active (up to a certain degree of substitution (DS) or DB) and that some insoluble aggregates are more stimulatory than the soluble polymers. The best conclusion at this time is that the immunopotentiating activity of (1→3)-β-d-glucans depends on a helical conformation and on the presence of hydrophilic groups located on the outside surface of the helix. Immunopotentiation effected by binding of a (1→3)-β-glucan molecule or particle probably includes activation of cytotoxic macrophages, helper T cells, and NK cells, promotion of T cell differentiation, and activation of the alternative complement pathway.