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A Comparison of Injected and Orally Administered β-glucans
Abstract
glucans have been extensively studied for their phar-macological effects. Despite in-depth research, little is known about the optimal dose and/or optimal route of appli-cation. In this paper, we are reporting the result of compar-ing the immunostimulating activities of four commercially available glucans differing both in their solubility and source. In addition, we compared intraperitoneal and oral application, and the differences between a single versus repeated doses. Our data showed strong differences in activities of indi-vidual glucans, with glucan yeast-derived #300 being the best, and grain-derived ImmuneFiber being the worst. Furthermore, we demonstrated that oral delivery of glucan resulted in significant immunological activity, which albeit slightly lower, corresponded with injectable application. Depending on the applied dose, the effects of individual glucans were long-lasting and in some cases, lasted up to two weeks. In conclusion, our report represents further evidence about differences among commercial glucans and shows that these biological response modifiers can be similarly active when used in both injectable and oral form.
... Extensive research in the last decade introduced four new types of glucan with improved purities and effectiveness that significantly stimulate several types of immune reactions oriented against microbes, toxic factors, cancer and other influences (8)(9)(10). Additional studies showed strong effects on hypertension, cholesterol levels, and arthritis (11). ...
... Salivary defense factors, including factors such as CRP and lysozyme, represent a significant part of mucosal immunity-particularly in immunodeficient patients (29) and children prone to respiratory infections (30). In this study we increased the experimental group described previously (6)(7)(8). Data obtained from this enlarged group confirmed our original data and again showed significant effect of β-glucan treatment. CRP levels, higher levels of which document more accute inflammation than persisting long-term inflammatory pressure (16,20). ...
... The decrease of these levels again reflects reduction of inflammation and lower transduction of this protein from capillaries to the saliva. Compared to our previous findings, we found an increase in albumin levels in control group, which reflects the fact that this particular group of children came to the Sanatorium with higher inflammatory load, most probably caused by worse climatic and environmental conditions from children's homes, where the pollution is significantly worse during spring and fall (6)(7)(8)18). These findings are further supported by the dynamics of the changes in calprotectin levels, where in control group we again found small increase, but the β-glucan treatment caused strong decrease in the level of calprotectin, which can be considered to be the most important finding of our study. ...
... Extensive research in the last decade introduced four new types of glucan with improved purities and effectiveness that significantly stimulate several types of immune reactions oriented against microbes, toxic factors, cancer and other influences (8)(9)(10). Additional studies showed strong effects on hypertension, cholesterol levels, and arthritis (11). ...
... Salivary defense factors, including factors such as CRP and lysozyme, represent a significant part of mucosal immunity-particularly in immunodeficient patients (29) and children prone to respiratory infections (30). In this study we increased the experimental group described previously (6)(7)(8). Data obtained from this enlarged group confirmed our original data and again showed significant effect of β-glucan treatment. CRP levels, higher levels of which document more accute inflammation than persisting long-term inflammatory pressure (16,20). ...
... The decrease of these levels again reflects reduction of inflammation and lower transduction of this protein from capillaries to the saliva. Compared to our previous findings, we found an increase in albumin levels in control group, which reflects the fact that this particular group of children came to the Sanatorium with higher inflammatory load, most probably caused by worse climatic and environmental conditions from children's homes, where the pollution is significantly worse during spring and fall (6)(7)(8)18). These findings are further supported by the dynamics of the changes in calprotectin levels, where in control group we again found small increase, but the β-glucan treatment caused strong decrease in the level of calprotectin, which can be considered to be the most important finding of our study. ...
Background:
The role of glucan in the stimulation of immune reactions is well established. In our report, we focused on the effects of orally administered glucan on nonspecific immunity of children with chronic respiratory problems.
Materials and methods:
We measured the levels of albumin, lysozyme. C-reactive protein (CRP) and calprotectin in the saliva of 60 children ages 8-12 years and evaluated the effects of 30-day treatment with 100 mg/d oral dose of glucan.
Results:
We found a significant increase in the production of lysozyme, CRP and calprotectin in glucan-treated children.
Conclusions:
Short-term oral application of natural immunomodulator β-glucan significantly stimulated mucosal immunity of children with chronic respiratory problems.
... For years, there was a controversy between the notions that water-insoluble glucans show only little biological activity, whereas soluble glucans are highly active. Similar questions whether orally-given glucan is as active as injected one has been solved only recently [5]. ...
... Krestin Mushroom Soluble Kureha Corp, Japan [5] ...
... However, it is important to keep in mind that these reviews are oriented towards comparing results of numerous publications and none of them offers a one-on-one comparison of several glucans. Very few studies tried to directly compare individual glucans and the number of used glucans was seriously limited [5] [7] [8]. ...
Glucans belong to a group of biologically active natural compounds called biological response modifiers. These substances represent highly conserved structural components of cell walls in yeast, fungi, grain and seaweed. The effects of -glucan on immune reactions are well established however direct comparisons of the biological activities of several individual glucans are extremely rare. As this paper will show, we tested sixteen different glucans and evaluated the possibility whether individual glucans will be similarly active against each of the tested biological properties or if each glucan will affect different reactions. No direct connection between source and immunological activities was found. Based on our results, we can conclude that highly purified and highly active glucans have pleotropic effects, whereas poorly iso-lated glucans have only average (if any) biological effect. INTRODUCTION 1,3-Glucan's role as an immunomodulator has been well documented for over 50 years. Initial interest in the immunomodulatory properties of polysaccharides was raised after experiments revealed that a crude yeast cell preparation stimulated macrophages via activation of complement [1]. Further work identified the immunomodulatory active com-ponent as 1,3-glucan [2]. -Glucans show notable physio-logical effects; this is their most important quality and the reason why so much attention has been focused on them. Numerous studies (currently more than 6,000 publications) have subsequently shown that 1,3-glucans, either particu-late or soluble, exhibit immunostimulating properties, in-cluding antibacterial and anti-tumor activities (for review see [3,4]). There are various natural sources of -glucans; however, they are most often prepared from fungal cell walls. Baker's yeast is the most common and likely the best raw material for glucan extraction. Additional sources of glucan involve mushrooms, grain and seaweed. Diverse data on comparison of structure, molecular size, and biological effects can be found in literature. For example, the antitumor activity of schizophyllan is supposedly conditioned by the triple helix presence and a molecular weight higher than 100 kDa. It is more than likely that the triple helix structure is not the sole effective form of -glucan, because alkalic treatment, used in most isolation procedures, destroys this structure. In addi-tion, the most recent opinions do not confirm the established ideas of the necessity of high molecular mass and branching of biologically active -glucans.
... Although elevated serum BG in DSS mice with oral glucans might be partly due to gut translocation of the administered glucans, there is technical difficulty in the identification of different BGs in blood samples. Then, the inflammatory impact of different forms of BGs was tested by direct injection in mice, and the BGs alone did not induce inflammation [74][75][76]. The injection of BG plus LPS enhanced serum cytokine elicitation (TNF-α and IL-6), with the highest potency observed with LPS combined with Pachyman, followed by LPS + WGP [10], while LPS + Oat-BG only elevated liver IL-10. ...
... This multiplicity of responsive cell types suggests in vivo opportunities for the greatly enhanced elicitation of proinflammatory cytokines in settings of co-exposure to PAMPs with different receptors and signal transduction cascades [22,79]. In macrophages, Pachyman and other BG (such as curdlan) demonstrated moderate to high proinflammatory effects among the different forms of BG [59,75], and LPS plus Pachyman induced even more profound inflammation than LPS alone. There was a similar downregulation of TLR-4 and Dectin-1 in LPS alone or LPS with any BG, possibly as a protective response against cell injury from LPS-elicited reactive oxygen species (ROS) [80]. ...
(1→3)-β-D-glucans (BG) (the glucose polymers) are recognized as pathogen motifs, and different forms of BGs are reported to have various effects. Here, different BGs, including Pachyman (BG with very few (1→6)-linkages), whole-glucan particles (BG with many (1→6)-glycosidic bonds), and Oat-BG (BG with (1→4)-linkages), were tested. In comparison with dextran sulfate solution (DSS) alone in mice, DSS with each of these BGs did not alter the weight loss, stool consistency, colon injury (histology and cytokines), endotoxemia, serum BG, and fecal microbiome but Pachyman–DSS-treated mice demonstrated the highest serum cytokine elicitation (TNF-α and IL-6). Likewise, a tail vein injection of Pachyman together with intraperitoneal lipopolysaccharide (LPS) induced the highest levels of these cytokines at 3 h post-injection than LPS alone or LPS with other BGs. With bone marrow-derived macrophages, BG induced only TNF-α (most prominent with Pachyman), while LPS with BG additively increased several cytokines (TNF-α, IL-6, and IL-10); inflammatory genes (iNOS, IL-1β, Syk, and NF-κB); and cell energy alterations (extracellular flux analysis). In conclusion, Pachyman induced the highest LPS proinflammatory synergistic effect on macrophages, followed by WGP, possibly through Syk-associated interactions between the Dectin-1 and TLR-4 signal transduction pathways. Selection of the proper form of BGs for specific clinical conditions might be beneficial.
... β-Glucans can be administered internally and externally in a number of different routes such as intravenous, intraperitoneal, or subcutaneous (parenteral) injections; orally; bathing; or as part of a cream [114][115][116]. Efficacies of different routes (intraperitoneal injection, bathing, and oral administration) have been tested. ...
... The orally delivered pathway is much slower and said to have a less profound effect than injectable methods. However, this is often a more practical method as β-glucans can simply be added to food/feed [94,115,[141][142][143]. For example, Rodriguez et al. [140] fed salmon a diet supplemented with β-glucan and found that the β-glucan diet potentiated the immune response to vaccine by increasing innate and adaptive immune responses through the transcription of key cytokine genes such as INF-γ and IL-12. ...
Administration of β-glucans through various routes, including immersion, dietary inclusion, or injection, have been found to stimulate various facets of immune responses, such as resistance to infections and resistance to environmental stress. β-Glucans used as an immunomodulatory food supplement have been found beneficial in eliciting immunity in commercial aquaculture. Despite extensive research involving more than 3000 published studies, knowledge of the receptors involved in recognition of β-glucans, their downstream signaling, and overall mechanisms of action is still lacking. The aim of this review is to summarize and discuss what is currently known about of the use of β-glucans in fish.
... Several sources of β-glucans exist: fungi, yeasts, bacteria, algae, and various plants. Studies have shown that immunomodulating potential differs between β-glucans due to their origin, purity, structure, branching level, solubility, and molecular conformation [5][6][7][8][9]. Studies have also shown that the β-glucans can yield similar activities when used in both injectable and oral forms [5]. ...
... Studies have shown that immunomodulating potential differs between β-glucans due to their origin, purity, structure, branching level, solubility, and molecular conformation [5][6][7][8][9]. Studies have also shown that the β-glucans can yield similar activities when used in both injectable and oral forms [5]. ...
Respiratory tract infections (RTIs) are the most common form of infections in every age category. Recurrent respiratory tract infections (RRTIs), a specific form of RTIs, represent a typical and common problem associated with early childhood, causing high indirect and direct costs on the healthcare system. They are usually the consequence of immature immunity in children and high exposure to various respiratory pathogens. Their rational management should aim at excluding other severe chronic diseases associated with increased morbidity (e.g., primary immunodeficiency syndromes, cystic fibrosis, and ciliary dyskinesia) and at supporting maturity of the mucosal immune system. However, RRTIs can also be observed in adults (e.g., during exhausting and stressful periods, chronic inflammatory diseases, secondary immunodeficiencies, or in elite athletes) and require greater attention. Biologically active polysaccharides (e.g., β-glucans) are one of the most studied natural immunomodulators with a pluripotent mode of action and biological activity. According to many studies, they possess immunomodulatory, anti-inflammatory, and anti-infectious activities and therefore could be suggested as an effective part of treating and preventing RTIs. Based on published studies, the application of β-glucans was proven as a possible therapeutic and preventive approach in managing and preventing recurrent respiratory tract infections in children (especially β-glucans from Pleurotus ostreatus), adults (mostly the studies with yeast-derived β-glucans), and in elite athletes (studies with β-glucans from Pleurotus ostreatus or yeast).
... Glucan is well known to be a significant stimulator of immune reaction and these effects were repeatedly observed regardless the route of administration [26] or animal species. For evaluation of the potential effects of our glucan samples on phagocytosis, we used polymer microparticles based on hydroxymethacrylate, which, due to their negative charge, guarantee minimal false positivity [15]. ...
... For evaluation of the potential effects of our glucan samples on phagocytosis, we used polymer microparticles based on hydroxymethacrylate, which, due to their negative charge, guarantee minimal false positivity [15]. Our results showed significant stimulation of phagocytosis by both peripheral blood monocytes and neutrophils, which is in agreement with previous finding in mice [26] and pigs [13]. ...
... Briefly, determinations of membrane surface receptor expression were carried out by quantification of fluorescence staining of cells isolated from the spleen with anti-mouse CD4, CD8 and CD19 conjugated with Fluorescein isothiocyanate (FITC). Following incubation with the antibodies, the cells were washed; stained cells were then counted by flow cytometry [23]. ...
... Studies conducted previously using the identical mouse strain and evaluating phagocytic activity of isolated spleen cells under an identical protocol reported stimulation by yeast and mushroom beta-glucans that were remarkably similar to the activities reported in these trials even though the beta-glucans were administered IP in the previous study versus the oral dosing regimen reported here. This observation is consistent with experiments where the relative efficacies of oral administration of beta-glucans versus IP injections were compared directly, showing stimulation of phagocytic activity to be comparable under both formats [23]. The adjuvant effect of a fucoidan has also been evaluated in recent human clinical trials examining antibody production in Japanese subjects over the age of 60 years, a population with a reduced adaptive immune response relative to younger patients. ...
A fucoidan with high ester sulfate content (38-40% by weight) has been isolated in a commercial scale process from Laminaria hyperborea harvested from the western coast of Norway. This is the first characterization of a fucoidan from this species of macroalgae. Ultra purified samples with negligible endotoxin levels were evaluated for cytokine expression in cultured human mononuclear cells. Initiators of the acute phase response were only moderately elevated while the chemotactic cytokine interleukin-8 increased significantly over baseline. Following oral dosing of mice with fucoidan, splenocytes showed significant increases in interleukin-2 expression and in phagocytic activity similar to effects by equivalent doses of yeast and mushroom derived (1,3/1,6)-ß-D-glucans. Adaptive immunity was also affected by fucoidan as evidenced by significant increases in antibody titers in mice vaccinated with ovalbumin. Combination treatments of fucoidan together with a yeast beta-glucan showed additive effects, but gave no indication of synergy. To our knowledge, this is the first report of the effects of combinations of fucoidan with a beta-glucan in in vivo evaluations.
... β-glucan is well known to be a significant stimulator of immune reaction, particularly of the cellular branch. These effects were repeatedly observed regardless the route of administration (29). For evaluation of the potential effects of our glucan on phagocytosis, we used synthetic polymer microparticles based on hydroxymethacrylate, known for their low negative charge and therefore minimal subjective error during evaluation (22). ...
... For evaluation of the potential effects of our glucan on phagocytosis, we used synthetic polymer microparticles based on hydroxymethacrylate, known for their low negative charge and therefore minimal subjective error during evaluation (22). Our results showed significant stimulation of phagocytosis by both peripheral blood monocytes and neutrophils, which is in agreement with previous finding in mice (29). ...
Background:
In face of the challenge of the emergent diseases and the current efforts of the governments to create conditions to ban growth-promoting antibiotics and to improve efficiency of the commercial farming, new opportunities are created for natural, highly effective and cost affordable immunomodulators; able to induce and enhance resistance against diseases and to reduce farming-related stress. Supplementation of animal feed with β(1-3)(1-6)-D-glucans has been repeatedly shown to modulate the immune system ant to influence growth characteristics of farmed animals.
Materials and methods:
In our study we focused on evaluation of effects of an insoluble, fungi-derived β(1-3)(1-6)-D-glucan as dietary supplement in piglets. We measured the growth, phagocytosis of peripheral blood cells and interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) production after feeding with 15 mg of glucan/kg/day.
Conclusions:
Following supplementation, β(1-3)(1-6)-D-glucan has been shown to stimulate growth, phagocytic activity, and IL-2 production. In addition, it significantly lowered the cortisol and TNF-α levels after lipopolysaccharide (LPS) challenge.
... This active fragment binds to neutrophil CR3, priming effector cells to destroy tumour cells via a CR3-Syk-PI3K signalling cascade, demonstrating that immunological modulation requires β-glucan breakdown into active fragments [103]. Additionally, although I.P. injection of β-glucans has been investigated less than oral administration, several findings demonstrate that I.P. injection has more influence over immunological activity than oral administration [104,105]. ...
β-glucans are a large class of complex polysaccharides with bioactive properties, including immune modulation. Natural sources of these compounds include yeast, oats, barley, mushrooms, and algae. Yeast is abundant in various processes, including fermentation, and they are often discarded as waste products. The production of biomolecules from waste resources is a growing trend worldwide with novel waste resources being constantly identified. Yeast-derived β-glucans may assist the host’s defence against infections by influencing neutrophil and macrophage inflammatory and antibacterial activities. β-glucans were long regarded as an essential anti-cancer therapy and were licensed in Japan as immune-adjuvant therapy for cancer in 1980 and new mechanisms of action of these molecules are constantly emerging. This paper outlines yeast β-glucans’ immune-modulatory and anti-cancer effects, production and extraction, and their availability in waste streams.
... Though IP injection of β-glucan has been less extensively studied than oral administration, there are some studies, which show that IP injection has more profound effects on immunological activity than does oral administration [48]. According to one study, using a triple helical β-1,6-branched β-1,3-glucan purified from Lentinus edodes, or a shitake mushroom, it was found that IP injection of the β-glucan resulted in activation of peritoneal macrophages showing increased TNFα production, and proliferation of peritoneal macrophages, whole spleen cells and lymphocytes. ...
An increased understanding of the complex mechanisms at play within the tumor microenvironment (TME) has emphasized the need for the development of strategies that target immune cells within the TME. Therapeutics that render the TME immune-reactive have a vast potential for establishing effective cancer interventions. One such intervention is β-glucan, a natural compound with immune-stimulatory and immunomodulatory potential that has long been considered an important anti-cancer therapeutic. β-glucan has the ability to modulate the TME both by bridging the innate and adaptive arms of the immune system and by modulating the phenotype of immune-suppressive cells to be immune-stimulatory. New roles for β-glucan in cancer therapy are also emerging through an evolving understanding that β-glucan is involved in a concept called trained immunity, where innate cells take on memory phenotypes. Additionally, the hollow structure of particulate β-glucan has recently been harnessed to utilize particulate β-glucan as a delivery vesicle. These new concepts, along with the emerging success of combinatorial approaches to cancer treatment involving β-glucan, suggest that β-glucan may play an essential role in future strategies to prevent and inhibit tumor growth. This review emphasizes the various characteristics of β-glucan, with an emphasis on fungal β-glucan, and highlights novel approaches of β-glucan in cancer therapy.
... In addition, the meta-analysis of Talati et al. [50] proved that a median β-glucan dose of 7 g/day could reduce LDL cholesterol levels by 0.26 mM L -1 ., while another metaanalysis of AbuMweis et al. [51] demonstrated that LDL cholesterol was lowered by 0.27 mM L −1 following a median β-glucan dose of 5 g/day. In a comparison of administration methods of four βglucan products extracted from different sources in mice, Vetvicka and Vetvickova [52] reported that the individual product extracted from yeast cell walls was the best for immune-stimulating activities, and these activities in mice administrated with an intraperitoneal injection was slightly lower than those in mice supplemented by oral application. These authors also concluded that the somehow lower effects after oral stimulation could be easily overcome by repeated oral doses. ...
: Water-soluble and low molecular weight (Mw) β-glucans were successfully prepared by γ-irradiation of water-insoluble yeast β-glucans. The radiation dose used for the degradation of yeast β-glucan was remarkably reduced by increasing the pH of the sample or combining with hydrogen peroxide treatment. Radiation-degraded β-glucans with molecular weights in the range of 11−48 kDa reduced the total cholesterol, triglyceride, low density lipoprotein (LDL) cholesterol, and glucose levels in the blood of administered mice. The decreasing levels of both lipid and glucose indexes in the blood of tested mice strongly depended on the molecular weight of the β-glucan, and the radiation-degraded β-glucan with a molecular weight of about 25 kDa was found to be the most effective for the reduction of blood lipid and glucose levels. Particularly, the oral administration of 25 kDa β-glucan, with a daily dose of about 2 mg per head, reduced the total cholesterol, triglyceride, LDL-cholesterol, and glucose levels in the blood of tested mice to about 47.4%, 48.5%, 45.7%, and 47.2%, respectively. The effects on the reduction of blood lipid and glucose levels were also found to be stable after 20 days of stopping administration. These results indicate that the degraded β-glucan with a molecular weight of about 25 kDa prepared by γ-ray irradiation is a very promising ingredient that can be used in nutraceutical food for therapeutics of diabetic and dyslipidemia.
... For some time, it was even suggested that orally-administered glucan could not have any activity, because the human gastrointestinal tract lacks the enzyme necessary to break down the glucan molecule. This false hypothesis was pushed around without any scientific proof and was later corrected by studies directly comparing the effects of injected and orally used glucan [96]. Later studies revealed that the main route for a particular antigen to the body is through M cells localized within Peyer patches, which are considered to be the main site of entry, largely due to their intimate localization with the intestinal lumen. ...
... For some time, it was even suggested that orally-administered glucan could not have any activity, because the human gastrointestinal tract lacks the enzyme necessary to break down the glucan molecule. This false hypothesis was pushed around without any scientific proof and was later corrected by studies directly comparing the effects of injected and orally used glucan [96]. Later studies revealed that the main route for a particular antigen to the body is through M cells localized within Peyer patches, which are considered to be the main site of entry, largely due to their intimate localization with the intestinal lumen. ...
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.
... For a review dedicated to the molecular interaction of glucan with receptors, see (Legentil et al., 2015). The confusion regarding the effects of various route of administration was fi nally resolved by studies carefully comparing the effects after individual routs of administration and showing that the effects are the same (Vetvicka & Vetvickova, 2008;Vojtek et al., 2017). The development of an entirely new class of antiparasitic drugs is rare and lately seems to be near impossible. ...
Immunosuppression caused by parasitic infections represents the foremost way by which the parasites overcome or escape the host's immune response. Glucan is a well-established natural im-munomodulator with the ability to signifi cantly improve immune system, from innate immunity to both branches of specifi c immunity. Our review is focused on the possible role of glucan's action in antiparasite therapies and vaccine strategies. We concluded that the established action of glucan opens a new window in treatment and protection against parasitic infections.
... Despite numerous interesting reviews summarizing the current knowledge of glucan activities (24)(25)(26)(27), the best compare individual glucans against each other using identical experimental designs. In our previous studies, we directly compared over 50 individual glucans (12)(13)(14)(15)(16)18). However, the number of commercially available glucans has multiplied in many countries since, prompting us to compare the new batch of available glucans with glucan #300, which consistently showed the highest activities in the previous studies. ...
Background/aim:
β-Glucans are well-established immunomodulators with strong effects across all immune reactions. Due to the extensive amount of studies, glucans are steadily progressing from a non-specific immunomodulator to a licensed drug. However, direct comparisons of higher numbers of different glucans are rare.
Materials and methods:
In this study, we used 16 different glucans isolated from yeasts, mushroom, algae, and oat and compared their effects on phagocytosis, IL-2 production, antibody secretion, and inhibition of three experimental cancer models.
Results:
Our results showed significant differences among tested glucans, showing that despite the fact that glucans in general have strong stimulating effects on most aspects of the immune system, it is necessary to choose the right glucan.
Conclusion:
Based on our studies, we can conclude that highly purified and active glucans have significant pleiotropic effects.
... The problem of diverse data can be solved only by comparative studies. However, scientific reports directly comparing individual glucans are limited [11][12][13][14][15][16][17]. Readers interested in comparisons of glucan in cancer treatment should see the excellent review written by Story et al. [18]. ...
... The problem of diverse data can be solved only by comparative studies. However, scientific reports directly comparing individual glucans are limited [5,[8][9][10][11]. This led us to the current comparative review of 16 different commercially available glucans. ...
... It's clear that β-glucan has the ability to activate the phagocytic cells and increase their ability to engulf the dead yeast cells when the blood phagocytic cells interact with β-glucan. The phagocytosis is one of the mechanisms of the body defense against the pathogen; monocyte, macrophage and polymorphic nucleus cells are the main cells in this respect and they represent as the first line of the body defense, they found in most of the body tissues (Vetvicka and Vetvickova, 2008). β-glucanis one of the immune modulators especially that extracted from microorganisms. ...
β-glucans are naturally occurring polymers and their
biological and immunological effects are well
known. β-glucan was extracted from yeast cells
depending on alkaline – acid extraction method with
a net dry weight yield of 8.8%. Initial analyses
showed that the carbohydrates and proteins
contents were 44% 0.45% respectively. On the
other hand, results of FT-IR analysis confirmed that
the extracted β-glucan showed high degree of
similarity and purity as compared with the standard
with the absences of other carbohydrate
compounds like mannan and glycogen. Moreover,
we examined the structure of β-glucan with HPLC
and results indicated that the extracted β- glucan
had the same retention time as compared with the
standard β-glucan. Evaluating the in vivo antiangiogenic
effect of β-glucanby CAM assay was
carried using fertilized eggs with age of 8 days.
Different concentrations (250, 500, 750, 1000 and
1500 μg/ml) of β-glucan were used. Results showed
that increasing concentrations of β-glucan
significantly affect the neovascularization that cause
inhibition of the fertilized egg angiogenesis. The
human phagocytic function and mouse serum
vascular endothelial growth factor (VEGF) level
were indicated following the challenge with β-glucan
using the same concentrations. The results indicate
significant increase in phagocytosis rate up to 70%
and inhibitory effect on the production of mouse
VEGF serum level.
... Extensive research in this field yielded new types of glucan with higher purity and effectiveness that are able to significantly stimulate defense mechanisms not only against microbes but also toxic and other influences (Vetvicka and Vetvickova, 2008;. In addition, strong effects on hypertension, cholesterol levels, arthritis and blood sugar regulation were observed (Vetvicka and Vetvickova, 2007). ...
The role of glucan in stimulation of immune reactions has been studied for decades. In this report we focused on the effects of orally administered glucan in children with chronic respiratory problems. We measured the physical endurance using a 6MWT test and the levels of eNO in 50 children aged 8-12 years and evaluated the effects of 100 mg/d oral dose of glucan. We found significant improvements in physical indurance and exhaled nitric oxide in glucan-treated children. In addition, strong improvements in general conditions were found. Short-term oral application of natural immunomodulator β-glucan enhancers the overall health and regulation of energetic metabolism in children with chronic respiratory problems.
... The problem of diverse data can be solved only by comparative studies. However, scientific reports directly comparing individual glucans are limited [10][11][12][13][14][15], with only one really comprehensive study being published during last 5 years [16]. This led us to the current comparative review of 15 different commercially available glucans. ...
Biological and most of all immunological effects of natural immunomodulator glucan are already well established. However, since hundreds of individual glucans, isolated from various sources, used at different concentrations and having different physicochemical characteristics are being used, the current scientific knowledge is not complete. In addition, direct comparisons of individual glucans are quite rare. In the present paper, we tested fifteen varieties of glucans differing in source and solubility. Whereas no direct connection between source and immunological effects was found, we can conclude that the best glucans have pleiotropic effects stimulating all facets of immunological reactions, whereas other glucans have low effects or none at all.
... Numerous rodent studies demonstrated that glucan supplements offset the increased risk of infection, usually via stimulation of immunological activities (Davis et al., 2004). In addition, recent findings also showed strong effects on humoral immunity, including antibody formation (Vetvicka and Vetvickova, 2008;. Up to now, the effects of glucan on mucosal immunity has not been studied. ...
The role of glucan in stimulation of immune reactions has been well-established. In this report, we focused on the antibody production in glucan-supplemented children with chronic respiratory problems. We measured the levels of salivary IgA, IgM and IgG in 40 children aged 8-12 years and evaluated the effects of 100 mg d −1 oral dose of glucan. We found a significant increase in production of all tested antibodies in the glucan-stimulated group, but a decrease of antibody production in the control group. A thirty-day oral application of yeast-based natural immunomodulator β-glucan strongly stimulated the mucosal immunity of children with chronic respiratory problems.
... S. cerevisiae β-glucan is an established immunomodulator (9,10,12,21). β-Glucan belongs to a group of physiologically active materials, which are called biological response modifiers (22). Many studies have demonstrated that various forms of β-glucan exhibit antibacterial and antitumor activities (8,9,10,23,24). ...
Aim:
β-Glucan is one of the most abundant polymers in nature and has been established as an immunomodulator. This compound has notable physiological effects on mammalian immune systems, including anti-tumor and anti-infective activities and can activate the immune response. It is considered that the immune-stimulating activities of β-glucan can depend on physicochemical parameters, such as molecular size. Saccharomyces cerevisiae, also known as baker's yeast, is a frequently used source of β-glucan. The aim of the experiments was to investigate how different Saccharomyces cerevisiae β-glucan preparations with different molecular size affect interferon-gamma (IFN-γ) production in BALB/c mice.
Materials and methods:
In vivo and in vitro BALB/c mouse models were used for the investigations. Different β-glucan preparations were orally administrated in the in vivo experiments. IFN-γ production in BALB/c mice was analyzed by enzyme-linked immunosorbent assay and measuring interferon-γ RNA concentration.
Results:
The results showed that orally-administered β-glucan from S. cerevisiae enhanced IFN-γ production in BALB/c mice in the in vivo model, but not by mouse leukocytes in vitro. Moreover, water-soluble β-glucan enhanced IFN-γ production more effectively than did particulate β-glucan.
Conclusion:
IFN-γ plays an important role in immunity against viral and bacterial infections. Our experiments have shown that β-glucan preparations enhance IFN-γ production in BALB/c mice and can be potentially used for immune system stimulation in mammals. Current results may be used to develop soluble β-glucan nutritional supplements.
... The problem of diverse data can be solved only by comparative studies. However, scientific reports directly comparing individual glucans are limited [10][11][12][13][14][15], with only one really comprehensive study being published during last 5 years [16]. This led us to the current comparative review of 15 different commercially available glucans. ...
Biological and most of all immunological effects of natural immunomodulator glucan are already well established. However, since hundreds of individual glucans, isolated from various sources, used at different concentrations and having different physicochemical characteristics are being used, the current scientific knowledge is not complete. In addition, direct comparisons of individual glucans are quite rare. In the present paper, we tested fifteen varieties of glucans differing in source and solubility. Whereas no direct connection between source and immunological effects was found, we can conclude that the best glucans have pleiotropic effects stimulating all facets of immunological reactions, whereas other glucans have low effects or none at all.
... Series of studies showed that it stimulates the cellular and humoral branches of immune system (11), protects against mercury poisoning (12), positively influences levels of cholesterol and blood sugar (13), inhibits cancer growth (14), and potentiates wound healing (15,16). In addition, these effects were similarly profound when administered orally or intraperitoneally (17). Table 1 Mean concentration of C-reactive protein, albumin and lysozyme in saliva of children at baseline (day 1) and after completion of oral administration of glucan (day 30) The level of albumin in saliva at the beginning of the trial was elevated in both groups, which corresponds to the This is the first placebo-driven clinical study to assess the effects of orally-administered glucan in children with chronic respiratory problems. ...
Background:
The role of glucan in stimulation of immune reactions has been studied for several decades. In this report we focused on the effects of orally administered glucan in children with chronic respiratory problems.
Materials and methods:
We measured the levels of albumin, lysozyme and CRP in saliva of 40 children aged 8-12 years and evaluate the effects of 100 mg/d oral dose of glucan.
Results:
We found a significant increase in production of changes in production of lysozyme and CRP in glucan-treated children. In addition, a strong improvement in general conditions was found.
Conclusions:
Short-term oral application of natural immunomodulator β-glucan stimulated mucosal immunity of children with chronic respiratory problems.
... In addition, it is clear that individual β(1-3)-D-glucans can be highly active in one particular part of immune reaction and mediocre in other parts of immune reaction. The only β(1-3)-D-glucan consistently showing the highest activity in all tested reactions was Glucan #300, which corresponded with the previous studies (Vetvicka and Vetvickova 2008. In addition, we showed that besides the well-established effects of β(1-3)-D-glucans on immune reactions, this natural immunomodulator has multiple pleiotropic functions such as inhibition of adipogenic differentiation and inhibition of acute inflammation. ...
Numerous types of β(1-3)-D-glucans have been isolated from almost every species of yeast, grain, and fungi. These products
have been extensively studied for their immunological and pharmacological effects. In this paper we evaluated the possibility
whether individual β(1-3)-D-glucans will have an activity in less studied areas such as adipogenesis and inflammation. Our
results showed that of the tested β(1-3)-D-glucans, yeast-derived insoluble Glucan #300, strongly inhibited adipogenic differentiation,
supported wound healing and significantly lowered skin irritation. The remaining β(1-3)-D-glucans were significantly less
active. Taken together, our study showed that with respect to natural β(1-3)-D-glucans, there is a clear yes-or-no effect
suggesting that highly purified and highly active β(1-3)-D-glucans will have pleiotropic biological impact, whereas poorly
isolated and/or less active β(1-3)-D-glucans will have only mediocre properties.
... Recently, an attempt was made to solve this problem using semisynthetic and synthetic probes suitable for accurate immunological research 9 . In addition, very few studies comparing various commercially available glucans exist 10,11 . ...
β-Glucans are well-established immunomodulators. Recently, glucans have been found to influence stress-related immunosuppression.
The aim of this study was to compare the effects of four different types of β-glucans on immune reactions suppressed by cold- or restrain-induced stress.
Mice were subjected to restraint and cold stress for various time intervals. The ability of individual glucans to overcome stress-related changes was evaluated after 14 days of feeding.
First, we showed that cold stress caused 38% decrease in phagocytic activity. While all glucans showed some ability to inhibit stress-related inhibition, only glucan #300 was able to return the phagocytosis to a normal level. In the control group, feeding with glucans did not alter the level of corticosterone. On the other hand, both types of stress resulted in a significant increase in corticosterone which was blocked to some extent by feeding with glucan. Both types of stress reduced IL-6 secretion but only glucan #300 managed to keep IL-6 secretion above control levels. The same results were obtained in the case of IL-12.
From our data, we can conclude that, even when all orally-administered glucans helped to restore the stress-related decrease in immune reaction, the level of activity varied widely among individual glucans. In addition, the results suggest that glucans might work via inhibition of corticosterone levels and/or stimulation of cytokine production.
This research aims to evaluate the effect of β glucan extracted from Candida albicans on the pathological effect of P. chrysogenum isolated from subclinical bovine mastitis from Abu Ghraib area in Baghdad by California mastitis test in winter 2020 on some internal organs such as (bone, brain, lung and intestine) by intramammary injection for two weeks then the beta-glucan extracted from the yeast Candida albicans was used for treatment of P. chrysogenum infection at two concentrations 50 and 100 mg/kg by two methods of injection (intramammary and intraperitoneal). The present study findings demonstrated different degrees of inflammation in these organs especially in the bone and brain, in addition, treatment with beta-glucan extracted from C. albicans showed a strong recovery response at a 50 mg/kg concentration by intraperitoneal injection in all organs from a 100 mg/kg concentration intraperitoneal injection was better than intramammary injection. Additionally, the results showed that the concentration of IgG was determined in serum samples of mice infected with P. chrysogenum using radial immunodiffusion plate, which showed different diameters of precipitation rings in the gel of plate with an increase in IgG concentration in all mice compared to the normal value of the concentration of IgG.
Humic acids are compounds resulting from decomposition of organic matter. Despite their common presence, our knowledge of their biological effects is limited, and current findings are controversial. We decided to evaluate the immunological effects of two different types of humic acids, differing in source and biochemical characteristics. Using both components either alone or in combination with the well-established yeast-derived immunomodulator glucan, we measured their effects on both the cellular (phagocytosis and tumor suppression) and humoral (antibody production and cytokine secretion) branches of immune reactions. In summary, our results suggest that humic acids are biologically active immunodulators affecting both the humoral and cellular branches of immune reactions. In addition, the two humic acids studied here are working in synergy in stimulation of the immune reaction, supporting further studies of these natural immunomodulators.
Beta-D-glucans belong to a group of natural, physiologically active compounds, generally called biological response modifiers. Glucans represent highly conserved structural components of cell walls in yeast, fungi, or seaweed. Despite long history of research, the exact mechanisms of glucan action remain unsolved. The present review starts with the history of glucans. Next, the detailed information about the possible glucan sources is followed by a description of the mechanisms of action. Physiological functions of glucan suggest the possible use of glucans not only as non-specific immunomodulator, but also as its possible future use as a drug.
Glucans, or polymers of D-glucose linked by (1→3)-β and (1→6)-β glycosidic linkages are the common polysaccharides of the fungal cell wall. They are usually located in the inner part of the wall and play the role of skeletal polysaccharide contributing to the shape and rigidity of the cell wall. The β-glucan molecules are interlinked by the hydrogen bonds and sometimes occur in a complex with other polysaccharides, such as chitin.β-Glucans isolated from the various yeast and fungal species may have different molecular weight or other structural parameters such as degree of branching or the length of the side-chains which may affect their solubility in water. Many fungal β-glucans possess remarkable ability to enhance the immune system, i.e. act as immunomodulators. Numerous studies have demonstrated the activity of β-glucans as biological response modifiers that are able to exert beneficial effect in host by demonstrating antitumor, antibacterial, antiviral and antiparasitic activities. Some studies have attempted to correlate biological activity of individual β-glucans to their spatial structure or helical conformation. However neither such correlation nor the precise mechanism of the activation of the immune system by β-glucans have been unambiguously proven.The present article reviews the existing knowledge on the immunological activity of the fungal β-glucans and provides some recent results on the radioprotective and antimutagenic activity of the β-glucan isolated from the baker's yeast.
Antitumor mAb bind to tumors and activate complement, coating tumors with iC3b. Intravenously administered yeast beta-1,3;1,6-glucan functions as an adjuvant for antitumor mAb by priming the inactivated C3b (iC3b) receptors (CR3; CD11b/CD18) of circulating granulocytes, enabling CR3 to trigger cytotoxicity of iC3b-coated tumors. Recent data indicated that barley beta-1,3;1,4-glucan given orally similarly potentiated the activity of antitumor mAb, leading to enhanced tumor regression and survival. This investigation showed that orally administered yeast beta-1,3;1,6-glucan functioned similarly to barley beta-1,3;1,4-glucan with antitumor mAb. With both oral beta-1,3-glucans, a requirement for iC3b on tumors and CR3 on granulocytes was confirmed by demonstrating therapeutic failures in mice deficient in C3 or CR3. Barley and yeast beta-1,3-glucan were labeled with fluorescein to track their oral uptake and processing in vivo. Orally administered beta-1,3-glucans were taken up by macrophages that transported them to spleen, lymph nodes, and bone marrow. Within the bone marrow, the macrophages degraded the large beta-1,3-glucans into smaller soluble beta-1,3-glucan fragments that were taken up by the CR3 of marginated granulocytes. These granulocytes with CR3-bound beta-1,3-glucan-fluorescein were shown to kill iC3b-opsonized tumor cells following their recruitment to a site of complement activation resembling a tumor coated with mAb.
Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.
Anti-tumor mAbs hold promise for cancer therapy, but are relatively inefficient. Therefore, there is a need for agents that might amplify the effectiveness of these mAbs. One such agent is beta-glucan, a polysaccharide produced by fungi, yeast, and grains, but not mammalian cells. Beta-glucans are bound by C receptor 3 (CR3) and, in concert with target-associated complement fragment iC3b, elicit phagocytosis and killing of yeast. Beta-glucans may also promote killing of iC3b-opsonized tumor cells engendered by administration of anti-tumor mAbs. In this study, we report that tumor-bearing mice treated with a combination of beta-glucan and an anti-tumor mAb show almost complete cessation of tumor growth. This activity evidently derives from a 25-kDa fragment of beta-glucan released by macrophage processing of the parent polysaccharide. This fragment, but not parent beta-glucan, binds to neutrophil CR3, induces CBRM 1/5 neoepitope expression, and elicits CR3-dependent cytotoxicity. These events require phosphorylation of the tyrosine kinase, Syk, and consequent PI3K activation because beta-glucan-mediated CR3-dependent cytotoxicity is greatly decreased by inhibition of these signaling molecules. Thus, beta-glucan enhances tumor killing through a cascade of events, including in vivo macrophage cleavage of the polysaccharide, dual CR3 ligation, and CR3-Syk-PI3K signaling. These results are important inasmuch as beta-glucan, an agent without evident toxicity, may be used to amplify tumor cell killing and may open new opportunities in the immunotherapy of cancer.
β-Glucan, a naturally occurring polysaccharide, is found mostly in the cell wall of fungi. In macroorganisms it acts as a potent biological response modulator. Its history began in the sixties of the last century, when it was found as a main component of zymosan as well as of extracts from medicinal Asian mushrooms. The review itemizes sources, structure, mechanisms of biological effects and adverse reactions of β-glucan and proposes alternatives of the future research.
β-Glucans are structural cell wall polymers of many fungi which possess immunomodulatory activities. Although the therapeutic benefits associated with these compounds, particularly as anti-infective and antitumorigenic agents, have led to a large body of published research over the last five decades, it is still unclear how these carbohydrates mediate their effects. Recent studies, however, are starting to shed some light on the cellular receptors and molecular mechanisms involved, which also have direct relevance on the innate immune response to fungal pathogens.
beta-glucans are pharmacologic agents that rapidly enhance host resistance to a variety of biologic insults through mechanisms involving macrophage activation. To determine whether stimulation of the beta-glucan receptors on human monocytes resulted in cytokine production, monolayers of monocytes were incubated with purified yeast glucan particles and measured for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) mRNA and protein. By Northern blot analysis, TNF-alpha mRNA was detected within 30 min of incubation with glucan particles, peaked at 2 h, and remained elevated for at least 8 h. Glucan induction of IL-1 beta mRNA followed a similar time-course of initiation and accumulation. By enzyme-linked immunosorbent assays (ELISAs), significant levels of TNF-alpha and IL-1 beta were present in supernatants of glucan-treated cells within 1 h and plateau levels of both cytokines were approached within 4 h. At particle-to-cell ratios of from 0.4 to 18, glucan particles induced dose-dependent increases in TNF-alpha and IL-1 beta mRNA and corresponding increases in TNF-alpha and IL-1 beta proteins. Exposure of monocytes to glucan particles for 0-30 min and washing before continued incubation for 4 h in particle-free buffer induced production and secretion of TNF-alpha and IL-1 beta in a time-dependent fashion compatible with phagocytosis. The pretreatment of monocyte monolayers with trypsin reduced glucan-induced production of TNF-alpha and IL-1 beta in a dose-dependent manner with 5 micrograms/ml of trypsin effecting reductions of greater than 50%. Thus, glucan particles induce human monocyte production of TNF-alpha and IL-1 beta by a mechanism that is dependent on trypsin-sensitive beta-glucan receptors.
The effect of intravenous administration of lentinan, an immunopotentiating polysaccharide, on the production of interleukin 1-alpha (IL 1-alpha), interleukin 1-beta (IL 1-beta) and tumor necrosis factor-alpha (TNF-alpha) by monocytes in peripheral blood mononuclear cells (PBM) was studied in patients with gastric carcinoma. Peripheral blood samples were obtained from 10 patients before and 3, 5 and 7 days after a single dose of 2 mg lentinan injection. The ability of monocytes in PBM to produce IL 1-alpha was significantly augmented 3 and 5 days after lentinan administration, as compared with that before treatment. IL 1-beta production was also significantly increased 3, 5 and 7 days after the drug injection. Further, the capacity to produce TNF-alpha was significantly enhanced 3, 5 and 7 days after the drug administration. Thus, it is likely that the augmentation of these cytokine's production may contribute to the antitumor action of lentinan in patients with gastric carcinoma.
Alpha-fetoprotein (AFP) was found to suppress the phagocytic activity of the blood monocytes and neutrophils in vitro. The amounts of AFP detectable by immunofluorescence in the livers of nu/nu, nu/+ and +/+ mice were quite comparable, and thus could not have been responsible for the alterations in phagocytosis found in leukocytes of athymic nude mice during their ontogenetic development.
The chemical structure and characteristics, the antitumour activity, the antibacterial, antiviral, antifungal, antiparasitic activities, immunological properties and mode of action of immunomodulators of microbial origin, especially antitumour polysaccharide lentinan, have been discussed immunopharmacologically in comparison with pachymaran, schizophyllan, DiLuzio's yeast glucan, Coriolus preparation PS-K, Streptococcal preparation OK-432, Nocardia rubra cell wall skeleton N-CWS together with BCG and Corynebacterium parvum. Lentinan exerts its inhibitory action not only on allogeneic tumours but also on syngeneic and autologous tumours, and prevents chemical and viral carcinogenesis. The phase III randomized control study of lentinan in cancer patients with gastric and colo-rectal cancer showed the clinical efficacy of lentinan in prolonging the life span and improving host immune responses. Experimental and clinical application demonstrated the advantage of N-CWS over BCG-CWS, and a recent study on OK-432 showed similar results to those obtained with C. parvum. In future work on microbial immunomodulators, it will be essential to find a parameter of the host-tumour relationship which will indicate the protocol for application of immunomodulators, and to find a new-type of selective immunostimulant. For this purpose, exhaustive studies on lymphokines, monokines and lymphocyte tropic hormones are indispensable.
The protective efficacy of glucan as an adjuvant with killed promastigotes of Leishmania donovani was compared with that of soluble or particulate fractions of the parasite. When these vaccine preparations were injected either intravenously or subcutaneously in CF-1 mice, glucan potentiated resistance against L. donovani infections as reflected by significant reductions in hepatic amastigote counts relative to infected control mice. The leishmanial antigens alone afforded no protection. Serum direct agglutination titers to leishmanial antigens were highest in all groups given the vaccine intravenously, whereas the delayed-type hypersensitivity response to the antigen was positive only in groups immunized subcutaneously with glucan as an adjuvant. Some index of protection and immune response against visceral infection with the parasite was seen in groups vaccinated with glucan and soluble antigens. However, the protection afforded by glucan and particulate antigens of L. donovani more closely paralleled the resistance of mice treated with glucan and unfractionated killed promastigotes. Further antigenic analysis of particulate fractions of L. donovani may optimize effective immunization when used with appropriate adjuvants, e.g., glucan.
A simple micromethod for testing human blood leukocyte phagocytosis employing synthetic hydrophilic particles based on 2-hydroxyethylmethacrylate is described. The normal level of phagocytosing leukocytes in healthy children was 20.1 +/- 2.7%, and in healthy adult donors 34.3 +/- 6.1%. The method was found suitable for routine testing in both clinical and laboratory practice.
The ability of grifolan (GRN), a purified fungal (1-->3)-beta-D-glucan, to induce various cytokines from macrophages was examined in vitro. Interleukin-6 (IL-6) activity in supernatants from the culture of macrophage cell line, RAW264.7 was dependent on increasing doses of GRN. The level of IL-6 induced with 500 micrograms/ml of GRN was comparable to that induced with lipopolysaccharide (LPS) 10 micrograms/ml. Enhancement of the mRNA level of IL-6 by treatment with GRN was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The effect of GRN on production of IL-6 was also observed using peritoneal macrophages from C3H/HeJ mice which did not respond to endotoxins. This data suggested that the ability of GRN to activate IL-6 production of macrophages is not due to contamination of endotoxins in the preparation. Enhanced production of cytokine by GRN was observed not only with IL-6, but also with interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). In the production of TNF alpha, GRN was more effective than LPS used in this study. Other soluble or gel-forming(1-->3)-beta-D-glucans from various sources did not enhance the production of such cytokines although they are structurally similar to GRN. The above results indicate that GRN is a novel macrophage activator which augments cytokine production without dependence on endotoxins.
ICR mice were treated with a carcinogen, N-butyl-N'-butanolnitrosoamine BBN), every day for 8 consecutive weeks and the effects of oral administration of edible mushrooms on the induction of urinary bladder carcinoma and on the activities of macrophages and lymphocytes were studied. Bladder carcinoma were found in all 10 mice (100%) treated with BBN alone, while we observed carcinoma only in 9 of 17 mice (52.9%), in 7 of 15 mice (46.7%) and 13 of 20 mice (65.0%) treated with Lentinus edodes, Grifola frondosa and Pleurotus ostreatus, respectively. Chemotactic activity of macrophages was suppressed in mice treated with BBN alone but maintained almost the normal level in mice treated with BBN plus Lentinus, Grifola or Pleurotus. Lymphocytes collected from mice treated with BBN plus each mushroom showed almost normal blastogenic response against concanavalin A, although those from mice treated with BBN alone completely retarded their response. Cytotoxic activity of lymphocytes against Yac-1 cells was also maintained at a normal level in mice treated with BBN plus each mushroom. Whereas in mice treated with BBN alone significant depression of NK cell activity occurred. Significantly higher cytotoxic activity against P-815 cells was observed in lymphocytes from mice treated with BBN plus each mushroom than that in lymphocytes from normal mice or mice treated with BBN alone.
Medicinal properties have been attributed to mushrooms for thousands of years. Mushroom extracts are widely sold as nutritional supplements and touted as beneficial for health. Yet, there has not been a critical review attempting to integrate their nutraceutical potential with basic science. Relatively few studies are available on the biologic effects of mushroom consumption, and those have been performed exclusively in murine models. In this paper, we review existing data on the mechanism of whole mushrooms and isolated mushroom compounds, in particular (1-->3)-beta-D-glucans, and the means by which they modulate the immune system and potentially exert tumor-inhibitory effects. We believe that the antitumor mechanisms of several species of whole mushrooms as well as of polysaccharides isolated from Lentinus edodes, Schizophyllum commune, Grifola frondosa, and Sclerotinia sclerotiorum are mediated largely by T cells and macrophages. Despite the structural and functional similarities of these glucans, they differ in their effectiveness against specific tumors and in their ability to elicit various cellular responses, particularly cytokine expression and production. Unfortunately, our data base on the involvement of these important mediators is still rather limited, as are studies concerning the molecular mechanisms of the interactions of glucans with their target cells. As long as it remains unclear what receptors are involved in, and what downstream events are triggered by, the binding of these glucans to their target cells, it will be difficult to make further progress in understanding not only their antitumor mechanisms but also their other biological activities.
This paper summarizes the structure, biological activities, signaling, and metabolic degradation of fungal beta-1,3-glucans. Fungal beta-glucans exist both soluble and particulate forms. Conformation of the soluble beta-glucan was classified into three groups: triple helix, single helix and random coil. Fungal beta-1,3-glucans exhibit a variety of biological and immuno-pharmacological activities, and the significance of these activities is dependent on the structure, such as solubility in water, molecular weight, degree of branching, and conformation. Many of the activities, such as nitrogen oxide synthesis of macrophage and limulus factor G activation, were dependent on the conformation, but some of the others were independent, such as interferon-gamma and colony stimulating factor syntheses. These activities are beneficial and pharmacologically useful, while some strongly related to allergic and inflammatory adverse reactions. It should be noted that the beta-glucans, once administered into the body, remain mainly in the liver and spleen for a very long period of time. The activity, at least in part, is maintained during these periods. The biochemical mechanisms of the beta-glucan, especially in soluble form, mediating biological activity was still not clearly demonstrated.
Glucans have a long history as nonspecific biological modulators. A novel glucan-Phycarine-was isolated from sporophytes of Laminaria digitata. Phycarine showed significant stimulation of phagocytic activity as well as potentiation of synthesis and release of IL-1, IL-6 and TNF-alpha. In addition, Phycarine increased NK cell-mediated killing of tumor cells both in vitro and in vivo while acting via complement receptor type 3 (CR3) receptors.
Beta-glucans, biological response modifiers (BRMs) derived from the cell walls of yeast and other sources, have been demonstrated to prime leukocyte complement receptor 3 (CR3), thus enabling these cells to kill tumours opsonised with complement fragment iC3b. Many tumours activate complement via the classical pathway mediated by antitumour monoclonal antibodies (mAbs) or natural antibodies. Studies into the cellular and molecular mechanisms of action have demonstrated that orally administrated yeast beta-glucans are ingested and processed by macrophages. These macrophages secrete the active moiety that primes neutrophil CR3 to kill iC3b-opsonised tumour cells. Extensive studies in preclinical animal tumour models have demonstrated the efficacy of combined oral particulate yeast beta-glucan with antitumour mAb therapy in terms of tumour regression and long-term survival. It is proposed that the addition of beta-glucan will further improve the clinical therapeutic efficacy of antitumour mAbs in cancer patients.
(1-->3)-beta-D-Glucans represent highly conserved structural components of cell walls in yeast, fungi, or seaweed. However, it is still unknown how they mediate their effects. The aim of this study was to evaluate both intraperitoneal and oral application of seaweed-derived (1-->3)-beta-D-glucan Phycarine. Phycarine showed significant stimulation of phagocytosis by peripheral blood cells. In addition, the efficiency of chemotherapy of Lewis lung carcinoma with cyclophosphamide was potentiated by Phycarine administration. Phycarine also strongly shortened the recovery of leucopenia caused either by chemotherapy or irradiation. Besides the role in stimulation of cellular immunity, we also found a significant increase of antibody formation. Using a suckling rat model for evaluation of the absorption and tissues distribution of enterally administered (125)I-Phycarine, we found that the majority of Phycarine was detected in the stomach and duodenum 5 min after the administration. This amount sharply decreased during first 30 min. A significant amount of Phycarine entered proximal intestine in a shortly after the gavage. Its transit through proximal intestine was decreasing with time and simultaneously increasing in the ileum. Systemic blood levels were very low (less than 0.5%). Taken together, these observations suggest that Phycarine is similarly effective both after i.p. and oral application, has very strong stimulating effects on three types of experimentally induced leucopenia and stimulates both humoral and cellular branch of immune reactions. The majority of Phycarine can be detected throughout the gastrointestinal tract, supporting the feasibility of enteral administration of Phycarine in the treatment of gastrointestinal diseases.
Numerous types of glucans have been isolated from almost every species of yeast, grain, and fungi. These products have been extensively studied for their immunological and pharmacological effects.
In this paper we evaluated the possibility whether individual glucans will be similarly active against each of the tested biological properties or if each glucan will affect different reactions.
Immunological effects of glucans were measured by evaluation of phagocytosis of HEMA particles by peripheral blood leukocytes and production of IL-2 by mouse splenocytes. Next we measured the effects of long-term treatment with glucan on levels of blood glucose and blood cholesterol. Four different glucans differing in origin (yeast, grain and mushroom) were used.
Our results showed that the same glucan, yeast-derived insoluble #300 glucan, stimulated phagocytosis of peripheral blood leukocytes, production of IL-2 by mouse splenocytes, lowered the cholesterol levels in mice with experimentally-induced cholesterolemia and lowered the level of blood sugar after induced hyperglycaemie. The remainder of tested glucans were only marginally active.
Taken together, our study showed that with respect to natural glucans, there is a yes-or-no effect suggesting that highly purified and highly active glucans will have pleiotropic impact, whereas poorly isolated and/or less active glucans will have only mediocre biological properties.
Immunostimulating properties of two different b-glucans isolated from Maitake mushrooms (Grifola frondosa)
- V Vetvicka
- J Vetvickova
Vetvicka V, Vetvickova J. Immunostimulating properties
of two different b-glucans isolated from Maitake mushrooms (Grifola frondosa). JANA. 2005; 8:33-39.