Anti-infectious and Anti-tumor Activities of ß-glucans.

BACKGROUND/AIM: The aim of this study was to directly compare the anti-infectious and anti-cancer effects of five commercially available glucans. MATERIALS AND METHODS: We used five different glucans isolated from algae, yeast, bacteria, oat, and mushroom. We compared their effects on the stimulation of phagocytosis of blood cells, on the secretion of IL-2, and on the inhibition of melanoma and breast and lung cancers. In addition, we evaluated the effects of glucan supplementation on two experimental models of infection. RESULTS: Most of the tested glucans stimulated phagocytosis and IL-2 secretion, reduced cancer growth, and ameliorated some effects of experimental infections. CONCLUSION: Glucans can produce significant pleiotropic effects, but the activity varies among individual samples.

Combination Therapy with Glucan and Coenzyme Q10 in Murine Experimental Autoimmune Disease and Cancer.

BACKGROUND/AIM: Coenzyme Q10 is a well-accepted anti-oxidant agent known to play a protective role in various physiological and disease processes. Recently, Coenzyme Q10 is gaining attention as a substance with significant anti-inflammatory properties. ß-Glucan is the most studied immunomodulator with significant synergetic effects with numerous bioactive molecules. We aimed to evaluate the possible synergistic effects of simultaneous use of coenzyme Q10 with the well-established immune modulator, ß-glucan, on immune reactions and cancer development. MATERIALS AND METHODS: Coenzyme Q10 and ß-glucan were used, both in vivo and in vitro, and their effects were evaluated using phagocytosis and cytokine secretion. RESULTS: Our study confirmed the strong anti-inflammatory effects of coenzyme Q10 and showed that these effects were further potentiated with the addition of ß-glucan. The anticancer effects of coenzyme Q10 were less pronounced, but stronger, with the addition of ß-glucan. CONCLUSION: There is significant synergy between coenzyme Q10 and ß-glucan.

Glucans and Cancer: Comparison of Commercially Available ß-glucans - Part IV.

BACKGROUND/AIM: ß-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.

Fucoidans Stimulate Immune Reaction and Suppress Cancer Growth.

BACKGROUND/AIM: Fucoidans are gaining popularity as natural immunomodulators. The aim of this study was to compare the immunological activities or both purified samples and commercially available mixtures containing fucoidan. MATERIALS AND METHODS: We evaluated the effects of various samples on phagocytosis, mitogenic response, natural killer (NK) activity, antibody formation and inhibition of breast cancer growth. RESULTS: We found significant immunostimulating activity, but the strength of these effects was different among individual samples. CONCLUSION: Fucoidans have strong immunostimulating potential, including inhibition of cancer, with isolated samples offering better activity than commercial mixtures.

Essential Oils from Thyme (Thymus vulgaris): Chemical Composition and Biological Effects in Mouse Model.

Thymus species are popular spices and contain volatile oils as main chemical constituents. Recently, plant-derived essential oils are gaining significant attention due to their significant biological activities. Seven different thymus-derived essential oils were compared in our study. First, we focused on their chemical composition, which was followed up by testing their effects on phagocytosis, cytokine production, chemotaxis, edema inhibition, and liver protection. We found limited biological activities among tested oils, with no correlation between composition and biological effects. Similarly, no oils were effective in every reaction. Based on our data, the tested biological use of these essential oils is questionable.

Addition of Selenium Improves Immunomodulative Effects of Glucan.

BACKGROUND: Selenium (Se) is an established essential nutrient that plays a role in various biological processes including cancer development. Similarly, stimulation of immune reactions by ß-glucans is well-documented. AIMS: In the current study, we focused on the stimulation of phagocytosis and interleukin (IL)-2 production and on potentiation of anticancer immunity by a combination of glucan with two types of Se. MATERIALS AND METHODS: Phagocytosis was evaluated using synthetic microspheres; cancer development was measured either using breast cancer cells or using lung cancer cells. RESULTS: Using two different murine models of cancer, we showed that the Se/glucan combination strongly suppressed the growth of cancer, mostly probably via stimulation of immunity. CONCLUSIONS: A combination of glucan with Se offers superior stimulation of immunity and inhibition of cancer growth.

Effects of curcumin on Helicobacter pylori infection.

BACKGROUND: Curcumin is a well-established natural molecule with significant biological and pharmaceutical effects. Its effects on Helicobacter pylori (H. pylori) infection have been repeatedly confirmed both in animal and human models. This study directly compared five different samples to evaluate if the effects are general or if they differ among samples. METHODS: Using a mouse model, we studied the effects of curcumin on lipid peroxide (LPO) level, myeloperoxidase (MPO) and urease activity, number of colonized bacteria, levels of anti-H. pylori antibodies, biofilm formation, IFN-γ, IL-4, gastrin and somatostatin levels in serum, and minimum inhibitory concentration. In addition, we evaluated the effects on biofilm production and antibacterial antibody response. RESULTS: In all tests, one sample (Sabinsa) was consistently the most active. CONCLUSIONS: All curcumin samples showed some anti-H. pylori effects, but only some of the tested samples had significant activity.

Glucan Supplementation Has Strong Anti-melanoma Effects: Role of NK Cells.

ß-Glucan is a natural immunomodulator consisting of glucose molecules. It is a well-established modifier with significant beneficial properties in infectious diseases and cancer therapy. Glucan effects on melanoma are relatively less studied, despite the increasing incidence of this type of cancer. In the current study, we focused on possible effects of insoluble yeast-derived ß-glucan on the growth of melanoma cells. We found that glucan supplementation had a strong-positive effect in both reducing tumor weight, lung colonies and overall survival rate of tested animals. In addition, glucan inhibited the damage to blood cells and potentiated the effects of regular chemotherapy. By using depletion of natural killer (NK) cells, we showed that these effects are, at least partly, mediated by direct action of glucan on NK cells.

Glucan supplementation enhances the immune response against an influenza challenge in mice.

BACKGROUND: The strong immunostimulating potential of ß-glucans has been well established in numerous diseases. However, the effects on viral infection were less studied. METHODS: In our study, we focused on possible effects of a special combined glucan formulation on immunosuppression caused by influenza infection. RESULTS: We found that a 2-week oral feeding with glucan mixture significantly reduced the effects of influenza infection in total mortality. Our study was focused on phagocytosis, cytokine levels, antibody response and cytotoxicity assay. CONCLUSIONS: Based on our data, we concluded that these effects are caused by stimulation of both cellular and humoral immune reaction resulting in lower viral load.

Immune-enhancing effects of Maitake (Grifola frondosa) and Shiitake (Lentinula edodes) extracts.

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 Maitake and Shiitake on immune reactions. MATERIALS AND METHODS: We measured phagocytosis, NK cell activity, and secretion of IL-6, IL-12, IFN-γ as well as C-reactive protein (CRP) after 14 days of oral application of tested glucans. For comparison, active hexose correlated compound (AHCC) was used in all reactions. RESULTS: We found significant stimulation of defense reaction. In all cases, the most active was the Maitake-Shiitake combination, with Maitake alone being the second strongest, followed by Shiitake on its own and AHCC. CONCLUSIONS: Short-term oral application of natural immunomodulating glucans from Maitake and Shiitake mushrooms strongly stimulated both the cellular and humoral branch of immune reactions. These activities were significantly higher than those of AHCC.

Anti-stress action of an orally-given combination of resveratrol, ß-glucan, and vitamin C.

Stress has repeatedly been found to reduce the abilities of the immune system to fight against individual attacks. The current dissatisfaction with classical medications has led to more attention being focused on natural molecules. As recent studies have suggested that some bioactive molecules can have synergistic effects in stimulation of immune system and reduction of stress, we have evaluated the stress-reducing effects of the resveratrol-ß-glucan-vitamin C combination. We found that compared to its individual components, this combination was the strongest reducer of stress-related symptoms, including corticosterone levels and IL-6, IL-12 and IFN-γ production.

Natural immunomodulators and their stimulation of immune reaction: true or false?

Natural immunomodulators are getting more and more popular. The popularity, however, often brings over-optimistic claims and mediocre effects. The purpose of the present study was to directly compare eleven most commonly used immunomodulators. Through testing both cellular and humoral branches of immune reactions, we found that most of the immunomodulators tested have limited, if any, effects, with glucan being consistently the most active molecule strongly stimulating every reaction evaluated. These data were also confirmed using a Lewis lung cancer model, where only glucan and resveratrol lowered the number of metastases.

Glucan­resveratrol­vitamin C combination offers protection against toxic agents.

Biological immunomodulators are routinely evaluated as a natural source of molecules with profound effects on the immune system. They belong to a group of physiologically active compounds, collectively termed biological response modifiers. Most of the studies were focused on immune system stimulation. Recently, they have become the focus of studies seeking molecules that are able to overcome negative effects of various immunotoxins. This paper concentrates on the effects of a glucan/resveratrol/vitamin C combination on immunosuppressive effects of mercury and perfluorinated hydrocarbons. Effects described in this review have strong clinical potential, as environmental contaminants have adverse effects on all aspects of the immune system and represent a serious threat to the health of both humans and animals.

Comparison of immunological properties of various bioactive combinations.

BACKGROUND: Lately, more and more preparation of various cocktails or mixtures of bioactive modulators have been introduced. Their true activity is, however, rarely tested. AIM: To compare six commercially available, glucan-based immunostimulators. METHODS: Immunological effects of tested combinations were measured by evaluation of phagocytosis of synthetic particles by peripheral blood neutrophils, production of IL-2 by mouse splenocytes, production of superoxide anion and nitrite oxide, antibody response to imunization with ovalbumin, and NK cell activity. RESULTS: Our results showed that with the exception of the highest doses (phagocytosis) and superoxide anion and nitrite oxide production, only RVB 300 showed significant immunostimulative activity. CONCLUSION: Based on our results, we can conclude that most of the tested natural immunomodulators have limited, if any, biological effects. Only RVB 300 significantly stimulated all six tested immunological reactions.

Combination of glucan, resveratrol and vitamin C demonstrates strong anti-tumor potential.

ß-Glucans are naturally occurring carbohydrates found in plants, fungi and some bacterial species, and currently are well-established and powerful immunomodulators with beneficial properties in cancer therapy. Recent studies suggested that some additional bioactive molecules have synergistic effects when combined with glucan. In the current study, we evaluated the anticancer properties of glucan, resveratrol, vitamin C combination. We found that compared to the individual components, the combination was the strongest activator of phagocytosis and antibody formation. Using two different models of cancer treatment, our results demonstrated that the combination strongly suppressed the growth of breast and lung tumors, most likely due to the stimulation of apoptosis.

Procathepsin D and cytokines influence the proliferation of lung cancer cells.

Enzymatically inactive procathepsin D (pCD) has been established as an important factor in the development of lung cancer. In addition to serving as a growth factor, pCD is also involved in communication between cancer cells and surrounding cells. In the present investigation, a possible combination of autocrine and paracrine actions of pCD was investigated. pCD initiated secretion of interleukin (IL)-4, IL-8, IL-10 and IL-13 from lung cancer cells. These cytokines participated in the proliferation of the cancer cells, as demonstrated both by adding the cytokines and by inhibition using specific anti-cytokine antibodies. Using several clones of lung cancer cells differing in production of activation peptide, the pCD/cytokine cooperation and action was shown to be dependent on pCD secretion. Further proof that pCD is one of the key molecules involved in cancer development is presented.

Immune enhancing effects of WB365, a novel combination of Ashwagandha (Withania somnifera) and Maitake (Grifola frondosa) extracts.

BACKGROUND: Stress has been found to significantly reduce the abilities of the immune system to fight infections. One of the ways to overcome the defects of the immune system is the strengthening of the defense reactions by nutrition. AIMS: TO EVALUATE IMMUNE ENHANCING EFFECTS OF THE FOLLOWING MATERIAL: WB365, a novel combination of Ashwagandha (Withania somnifera) and Maitake (Grifola frondosa) extracts. RESULTS: We found that both glucan-rich maitake extract and WB365 caused a similar stimulation of phagocytic activity. Stress-induced increase of corticosterone production was blocked by feeding with Ashwagandha extract and even more by WB365. Cytokine experiments showed that feeding with WB365 helped overcome the stress-related inhibition of IL-6, IL-12 and IFN-γ production. CONCLUSION: This study clearly demonstrated that WB365, a combination of Maitake mushroom-derived glucan and Ashwagandha extracts, has strong pleiotropic biological effects related to immune health and stress reduction.

Procathepsin D and cancer: From molecular biology to clinical applications.

Procathepsin D (pCD) is overexpressed and secreted by cells of various tumor types including breast and lung carcinomas. pCD affects multiple features of tumor cells including proliferation, invasion, metastases and apoptosis. Several laboratories have previously shown that the mitogenic effect of pCD on cancer cells is mediated via its propeptide part (APpCD). However, the exact mechanism of how pCD affects cancer cells has not been identified. Recent observations have also revealed the possible use of pCD/APpcD as a marker of cancer progression. The purpose of this review is to summarize the three major potentials of pCD-tumor marker, potential drug, and screening agent.

Effects of glucan on immunosuppressive actions of mercury.

Global cycling of mercury results in the presence of mercury salts in the environment. The well-established negative effects of mercury on the immune system led us to the study whether natural immunomodulator glucan can overcome the immunosuppressive effects of mercury. Two types of mercury, thimerosal and mercury acetate, were administered in a dose of 2-8 mg/L of drinking water to mice. After 2 weeks, all mice exhibited profound suppression of both cellular (phagocytosis, natural killer cell activity, mitogen-induced proliferation, and expression of CD markers) and humoral (antibody formation and secretion of interleukin-6, interleukin-12, and interferon-gamma) responses. The mice were then fed with a diet containing a standard dose of glucan. Our results showed that simultaneous treatment with mercury and glucan resulted in significantly lower immunotoxic effects of mercury, which suggests that glucans can be successfully used as a natural remedy of low-level exposure to mercury.

Beta-glucan-indomethacin combination produces no lethal effects.

BACKGROUND: The most important quality of beta-glucans and the reason why so much attention has been devoted to them are their physiological effects. They are typical biological response modifiers with pronounced immunomodulating activity. However, some questions about possible side effects remain. AIM: Several papers reported the lethal side effects of non-steroidal anti-inflammatory drugs in glucan-treated mice, probably due to the peritonitis by enteric bacteria. However, these results were never independently confirmed. The purpose of this study is to evaluate these claims using several different types of glucans. METHODS: Effects of combined treatment with four different types of glucans and indomethacin were measured by evaluation of phagocytosis of HEMA particles by peripheral blood leukocytes and production of IL-6 in mouse serum. In addition, the level of blood glucose, colon length and survival after 30 days of treatment was measured. RESULTS: Our finding showed that simultaneous treatment with glucan and indomethacin caused a small decrease of phagocytic activity and IL-2 production. Two other tested parameters-blood glucose levels and colon length-that had been found to be significantly affected by this treatment, were virtually unchanged. In the final, yet most important part of the study, we found absolutely no mortality, regardless of the type of glucan or the routes of glucan administration. CONCLUSION: No adverse negative effects due to simultaneous treatment with glucan and non-steroidal anti-inflammatory drug dose was found, despite testing two different routes of glucan administration and four different types of glucan.