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The Mushroom Agaricus Blazei Murill in Combination with Metformin and Gliclazide Improves Insulin Resistance in Type 2 Diabetes: A Randomized, Double-blinded, and Placebo-Controlled Clinical Trial
Abstract
Complementary and alternative medicine use in adults with type 2 diabetes is popular. Although most of the herbs and supplements appear to be safe, there is still insufficient evidence that demonstrates their definitive beneficial effects. This study was done to determine whether the supplement of Agaricus blazei Murill extract improves insulin resistance in type 2 diabetes.
This study was a clinical randomized, double-blind, placebo-controlled trial. Of a population of 536 registered diabetes patients with 72 subjects (1) aged between 20 and 75 years, (2) being Chinese, (3) having type 2 diabetes for more than 1 year, and (4) having been taking gliclazide and metformin for more than 6 months were enrolled in this study. The enrolled patients were randomly assigned to either receiving supplement of Agaricus blazei Murill (ABM) extract or placebo (cellulose) 1500 mg daily for 12 weeks. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as the major outcome measurement.
At the end of the study, subjects who received supplement of ABM extract (n = 29) showed significantly lower HOMA-IR index (3.6[standard deviation, 2.5] versus 6.6[standard deviation, 7.4], p = 0.04) than the control group (n = 31). The plasma adiponectin concentration increased 20.0(standard deviation, 40.7)% in the ABM group after 12 weeks of treatment, but decreased 12.0(20.0)% among those taking the placebo (p < 0.001).
Supplement of ABM extract improves insulin resistance among subjects with type 2 diabetes. The increase in adiponectin concentration after taking AMB extract for 12 weeks might be the mechanism that brings the beneficial effect. Studies with longer periods of follow-up should be conducted in the future.
... In a double-blind, placebo-controlled clinical study, 60 diabetic patients using gliclazide and metformin therapies were randomized for 1.5 g/day of A. blazei Murrill dried extract intake or placebo for 12-weeks intervention (Hsu et al., 2007). HOMA-IR index improved in the intervention group compared with placebo, with a concomitant increase in adiponectin concentrations. ...
... This may be because, even if chemotherapy is effective in treating cancer, the side effects easily lead to immunosuppression and deterioration in the QoL, that lead to abandoning this mode of treatments. Overall, the safety of mushrooms seems high, with few adverse effects (mainly gastrointestinal or skin reactions) easily reversible with the interruption of treatment, as already seen in some phase I trials cited above (Deng et al., 2009;Hsu et al., 2007;Twardowski et al., 2015). More in general, adverse event monitoring is an integral part of trials using mushrooms as an intervention (Sumiyoshi et al., 2010;Tsai et al., 2016). ...
... When the patient restarted taking the mushroom extract, the hepatic dysfunction emerged again. On the contrary, in a 1-year open-label, single-arm pilot study, 4 patients with hepatitis B took 1.5 g daily of an A. blazei Murrill mushroom extract (Hsu et al., 2007). There was an improvement of ALT and AST levels after the intervention trial, suggesting a hepatoprotective role of the mushroom extract. ...
Background
mushrooms are traditionally used as a food ingredient and in folk medicine. Many in vitro and animal studies have reported their potential health effects, but without any clear application in human health. Although they have a worldwide history of use in dishes and folk medicine, mushroom extracts are commonly taken as supplements but need to be evaluated regarding clinical effects and safety, in particular among patients searching for further efficacy for their disease beside pharmacological treatments already prescribed.
Scope and approach
this review summarizes available data from the scientific literature about the nutritional and effects of mushrooms on human health by selecting clinical studies on humans in English. At the same time, the safety profile and unwanted effects were highlighted.
Key findings and conclusions
in spite of their wide use among populations, data on humans were scant and did not justify extensive use without more well-designed trials on mushroom efficacy. Overall, their use seems to be safe, but with some side effects, easily reversible after intake interruption. Nutritional use seems promising for coping with the energy surplus of the Western countries and could be useful for some nutritional aspects.
... According to Tsujitani et al. [93], PSK is able to kill cancer cells. Methanol extracts of G. lucidum and G. tsugae decrease the proliferation of colorectal cancer cells over a 72-h period, according to a study by Hsu et al. [94]. This is accomplished by bringing the cell cycle to a halt in the G2/M phase, which is caused by increasing the amounts of p21 and p27 and decreasing the levels of cyclin A and B1 [94]. ...
... Methanol extracts of G. lucidum and G. tsugae decrease the proliferation of colorectal cancer cells over a 72-h period, according to a study by Hsu et al. [94]. This is accomplished by bringing the cell cycle to a halt in the G2/M phase, which is caused by increasing the amounts of p21 and p27 and decreasing the levels of cyclin A and B1 [94]. In vivo studies with human colorectal cancer cells demonstrated these results, which included a reduction in tumor growth, induction of cell death, and suppression of cell proliferation. ...
... Agaricus bisporus/White bottom mushroom flavonoids, alkaloids, terpenoids, and saponins decrease blood glucose and MDA levels as well as increase SOD activity [11,40] [42,43] hot air-dried powder hypoglycemic, decrease LDL-C level [44] fruiting body anti-obesity [30,45] ergothioneine antioxidant, cytoprotective [46,47] [48,49] gliclazide lowers HOMA-IR index increase plasma adiponectin [50] anti-cancer effects [51][52][53] Amillariella mellea polysaccharides lower fasting blood glucose, improve glucose intolerance and insulin resistance-decrease serum triglycerides, inhibit lipid accumulation [54] Antrodia cinnamomea (Syn. Antrodia camphorata) ...
... Antrodia cinnamomea similarly altered adipocyte function, as seen in the significantly decreased pro-inflammatory marker TNF-α, IL-1β, IL-6, and leptin levels, while adiponectin levels significantly increased in the treated groups compared to the non-treated high-fat diet-fed mice [56]. Twelve weeks of treatment with extract from Agaricus blazei Murill resulted in significantly decreased insulin levels and HOMA-IR in diabetic patients in parallel with significantly increased adiponectin levels [50]. The Mukitake mushroom Panellus serotinus significantly increased the serum adiponectin levels of db/db mice after a 4 week period of treatment compared to control-fed db/db mice. ...
In addition to conventional treatments, there is growing interest in preventive and complementary therapies. Proper nutrition can prevent the manifestation of several chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer, and can attenuate the severity of these diseases. Edible mushrooms have been used as nutrition and medicine for thousands of years. The spectrum and quantity of their medicinal compounds made them a widely investigated target both in basic research and clinical trials. The most abundant and medically important components are polysaccharides, terpenoids, phenols, and heterocyclic amines, but bioactive proteins, vitamins, including vitamin D, polyunsaturated fatty acids, and essential minerals are also important ingredients with noteworthy health benefits. Mushroom extracts have anti-diabetic, anti-hyperlipidemic, anti-inflammatory, antioxidant, cardioprotective, anti-osteoporotic, and anti-tumor effects and are well tolerated, even by cancer patients. In our previous review we detailed the molecular aspects of the development of type 2 diabetes, discussing the role of physical activity and diet, but we did not detail the role of medicinal mushrooms as part of nutrition. In this review, we aimed to summarize the most important medical mushrooms, along with their natural habitats, growing conditions, and components, that are presumably sufficient for the prevention and treatment of insulin resistance.
... Treatment with the polysaccharide GFP-N derived from Grifola frondosa improves IR in in vivo by regulating JNK and IRS1/PI3K signaling and GFP-N enhanced hepatic IR, lowering blood glucose levels, and protecting the kidneys and liver from damage (Chen et al., 2019c). According to a randomized doubleblind study by Hsu et al. (2007), treatment of human patients with T2DM with a combination of an extract from the mushroom A. blazei together with gliclazide and metformin for 12 weeks improved IR (Hsu et al., 2007). Furthermore, Yang et al. (2018) found administration of Lentinula edodes polysaccharides enhanced insulin production and lowered insulin resistance, while also improving gut microbiota dysbiosis, in insulin-deficient type 2 diabetic mice. ...
... Treatment with the polysaccharide GFP-N derived from Grifola frondosa improves IR in in vivo by regulating JNK and IRS1/PI3K signaling and GFP-N enhanced hepatic IR, lowering blood glucose levels, and protecting the kidneys and liver from damage (Chen et al., 2019c). According to a randomized doubleblind study by Hsu et al. (2007), treatment of human patients with T2DM with a combination of an extract from the mushroom A. blazei together with gliclazide and metformin for 12 weeks improved IR (Hsu et al., 2007). Furthermore, Yang et al. (2018) found administration of Lentinula edodes polysaccharides enhanced insulin production and lowered insulin resistance, while also improving gut microbiota dysbiosis, in insulin-deficient type 2 diabetic mice. ...
Diabetes mellitus is a prevalent metabolic and endocrine illness affecting people all over the world and is of serious health and financial concern. Antidiabetic medicine delivered through pharmacotherapy, including synthetic antidiabetic drugs, are known to have several negative effects. Fortunately, several natural polysaccharides have antidiabetic properties, and the use of these polysaccharides as adjuncts to conventional therapy is becoming more common, particularly in underdeveloped nations. Oxidative stress has a critical role in the development of diabetes mellitus (DM). The review of current literature presented here focusses, therefore, on the antioxidant properties of mushroom polysaccharides used in the management of diabetic complications, and discusses whether these antioxidant properties contribute to the deactivation of the oxidative stress-related signalling pathways, and to the amelioration of β-cell dysfunction and insulin resistance. In this study, we conducted a systematic review of the relevant information concerning the antioxidant and antidiabetic effects of mushrooms from electronic databases, such as PubMed, Scopus or Google Scholar, for the period 1994 to 2021. In total, 104 different polysaccharides from mushrooms have been found to have antidiabetic effects. Most of the literature on mushroom polysaccharides has demonstrated the beneficial effects of these polysaccharides on reactive oxygen and nitrogen species (RONS) levels. This review discuss the effects of these polysaccharides on hyperglycemia and other alternative antioxidant therapies for diabetic complications through their applications and limits, in order to gain a better understanding of how they can be used to treat DM. Preclinical and phytochemical investigations have found that most of the active polysaccharides extracted from mushrooms have antioxidant activity, reducing oxidative stress and preventing the development of DM. Further research is necessary to confirm whether mushroom polysaccharides can effectively alleviate hyperglycemia, and the mechanisms by which they do this, and to investigate whether these polysaccharides might be utilized as a complementary therapy for the prevention and management of DM in the future.
... Application of Oyster mushroom on these patients for 24 days constitutes 7 days mushroom,7 days no mushroom and then 7 days mushroom had revealed a decrease in systolic blood pressure (SBP, P< 0.01), diastolic blood pressure (DBP, p< 0.05) and both the plasma glucose (FPG & 2-hPG, p< 0.001) 76 . A clinical trial on antidiabetic efficacy of mushroom on 72 diabetic patients in Taiwan has been reported where capsule containing 500 mg Agaricus blazei was applied to patients at a dose of three times per day with gliclazide and metformin 77 . Patients subjected to this trial have shown low insulin resistance scores (HOMA IR) indicating their improvement in insulin resistance after 12 weeks 77 . ...
... A clinical trial on antidiabetic efficacy of mushroom on 72 diabetic patients in Taiwan has been reported where capsule containing 500 mg Agaricus blazei was applied to patients at a dose of three times per day with gliclazide and metformin 77 . Patients subjected to this trial have shown low insulin resistance scores (HOMA IR) indicating their improvement in insulin resistance after 12 weeks 77 . It has been reported that oral administration of Pleurotus ostreatus and P. cystidiosus to type 2 diabetes patients at dose 50 mg/kg/body weight upregulate the serum insulin levels and downregulate postprandial serum glucose levels 78 . ...
Diabetes mellitus is a highly complex disorder in which the blood glucose level is abnormally high because the body does not produce enough insulin to meet its needs. This disease is now highly life-threatening across the world and needs proper, low cost and easily available medication without or fewer side effects. At present, there are many synthetic hypoglycemic agents used in the treatment of diabetes but they fail due to harmful side-effects. Scientists are now aiming at mushrooms as they are known for a traditional repository of natural bioactive compounds which may have a potential antidiabetic effect. Many reports documented so far of the efficacy of bioactive metabolites isolated from mushrooms and their cultured mycelia that have shown to be successful in the treatment of diabetes. This study aims to review those bioactive metabolites showing antidiabetic potential resourcing from mushrooms. Relevant literature found in electronic databases and published during 1995-2020 was studied. The study reveals that bioactive metabolites isolated from mushrooms like polysaccharides, proteins, dietary fibers and many pharmacologically active compounds and different solvent extracts of mushrooms with unknown metabolites have been reported to possess antidiabetic potential both in vivo and in vitro studies, though only very few are on clinical trials. Out of thirty-nine reported mushroom species having antidiabetic efficacy, three genus Pleurotus, Grifola and Agaricus show the highest number of research publications. This review is focused on the current status and future possibilities of bioactive metabolites resourcing from medicinal mushrooms in the treatment of diabetes.
... 46 The effects of mushroom supplements on insulin resistance may also extend to people with diabetes. Hsu et al. 47 performed a small randomized double-blind placebo-controlled trial assessing the effects of A. blazei extract in people with type 2 diabetes mellitus. Participants received the mushroom extract at a dose of 1500 mg, or a placebo, daily for 12 weeks. ...
... In addition, plasma adiponectin (a protein hormone secreted by adipocytes, which helps regulate glucose and lipid metabolism and enhance insulin sensitivity) significantly increased by 20% in the mushroom group, whereas it decreased in the placebo group by 12% (P < 0.001). 47 Mushroom supplements may also benefit people with cardiovascular disease (CVD). In a small 2018 clinical trial (N 5 71), people with either high risk or stable angina were given a freeze-dried PSP extract of G. lucidum containing 180 mg b-d-glucan. ...
... PSK is directly cytotoxic to cancer cells [125]. Studies by Hsu et al., [126] show that methanol extracts of G. lucidum and G. tsugae inhibit colorectal cancer cell growth within 72 hours by downregulating cyclin A and B1, upregulating p21 and p27, arresting the cell cycle in G2/M, and suppressing tumor growth, inducing cell death, and inhibiting cell proliferation in human colorectal cancer cells in vivo. Mushroom extracts inhibit NF-kB transactivation in Caco-2 cells, with A. blazei Murill and Coprinus comatus showing the most significant reduction in NF-kB transactivation, causing tumor cells to cease proliferating, die, or become susceptible to antitumor agents [99,127]. ...
Rationale: A wide range of bioactive phytoconstituents from edible fungi, especially therapeutic mushrooms, have the potential to improve health, especially in the case of chronic illnesses. Known for its anti-cancer qualities, ganoderma lucidum has been the focus of multiple clinical studies. Existing systematic reviews imply that more clinical research and methodological refinement are necessary to support its usage as a primary cancer treatment.
Objective: The objective of this research is to evaluate the anti-cancer potential of the bioactive phytoconstituents found in mushrooms, specifically Ganoderma lucidum, in a thorough manner. The aim is to conduct a critical assessment of the extant literature, pinpoint any deficiencies, and offer valuable perspectives on the methodological excellence and research requirements in this domain.
Method(s): A thorough analysis of published clinical trials was carried out, with a focus on studies that examined the effectiveness of Ganoderma lucidum and other products derived from mushrooms in treating cancer. The study's design, stated results, and methodological rigor were all carefully examined to evaluate the validity and reliability of the conclusions.
Results: Despite Ganoderma lucidum's potential against cancer, the evaluation finds insufficient data to support its widespread usage as a primary cancer treatment. Products made from mushrooms, which are frequently sold as dietary supplements, have anti-cancer claims. But since pre-approval is not required under US regulatory framework in order to market food supplements, these statements raise questions regarding their scientific validity.
Conclusions/Recommendations: The study's result emphasizes the necessity of more methodological advancement in clinical studies examining Ganoderma lucidum's potential as an anti-cancer agent. It also highlights the significance of thorough scientific validation for goods made from mushrooms that make health claims. To establish accurate claims regarding their anti-cancer effects, recommendations include developing technological methods for the purification of bioactive substances and undertaking thorough studies of mushroom products from different geographical regions. The goal of this thorough analysis is to direct future investigations and support the ethical promotion and use of products derived from mushrooms for medical purposes.
... Dried extract of A. sylvaticus increased the immunity of patients with colorectal cancer (Fortes et al., 2008) and improved health status of postsurgical patients with colorectal cancer (Fortes et al., 2009); dietary supplementation with this mushroom (scaly wood mushroom) in form of dried extract reduced adverse side-effects of anticancer drugs improving gastrointestinal functions in patients with breast cancer treated with chemotherapy or radiotherapy (Valadares et al., 2013). Encapsulated extract from dried mushrooms Agaricus blazei increased insulin resistance in patients with type 2 diabetes (Hsu et al., 2007). ...
Introduction. Mushrooms have been consumed since
earliest times and have been recognized for their attractive
sensory and culinary attributes; besides, they contain high
amounts of bioactive and health-promoting compounds. This
review is devoted to wild edible mushrooms and their role in
the life of modern man.
Materials and methods. Literature research using
scientific publications on the topics related to wild mushrooms
as a food resource, their applications in medicine and
pharmaceuticals, as well as the methods for mushroom
cultivation was conducted.
Results and discussion. Wild edible mushrooms have high
nutritional value, contain high-quality proteins, fiber, essential
fatty acids, vitamins, including D2, microelements, as well as
valuable compounds such as polyphenols, terpenoids, sterols,
while having a low energy value, which makes it possible to
use them in cooking and in low-calorie diets. Wild edible
mushrooms have various specific pharmaceutical properties
that can be used in the treatment of various serious diseases.
The gathering and use of wild edible mushrooms for food make
a significant contribution to both the solution of the global food
shortage crisis and economics of different countries around the
world, and could be considered in some countries as new
sources of income for local people. The increase of interest on
mushroom consumption along human history at worldwide
level has led to the development of basic and sophisticated
techniques for their cultivation. Solid-state and submerged
liquid fermentations are nowadays useful methods for
cultivation of mushroom in a large-scale for production of
volumes of biomass and of valuable specific bioactive
metabolites. An interesting and unusual method to grow edible
mushrooms of Ustilago maydis, which are considered a
delicacy produced by the natural infection of the maize ears, is
described.
Conclusions. The role that the mushroom kingdom plays in
human life is extremely important and varied. In the near
future, their role in local economies around the world and as
raw materials for food and pharmaceutical products, including
industrial cultivation, will be areas of greatest use.
... However, from this study, it can be concluded that the bioactive compounds of this edible mushroom studied have the binding capacity to the insulin receptors and MHC class 1 protein with the potentiality of potent drug candidates as well. A significant improvement in insulin resistance was found in edible mushroom (Agaricus blazei)-treated individuals, and it may be due to an increase in plasma adiponectin concentration [25]. The effect of cooked button mushrooms (100 gm/day) as a diet on gestational diabetes was observed by Sun and Niu [6] and Venturella et al. [8]. ...
The mushrooms are highly nutritious and have numerous physiological properties and are beneficial due to their medicinal value. Several clinical studies showed the antidiabetic and antimicrobial roles of edible mushrooms. The study of the affinity of the bioactive molecules obtained from edible mushrooms with the insulin receptors is important in this context. The bioactive compounds of Pleurotus sajor-caju, an edible mushroom have been used for the present study. In this study, the molecular basis for selective affinity for the insulin receptor (1GAG) and the major histocompatibility (MHC) class 1 protein (1CE6) with some bioactive molecules namely C 22 H 34 O 4 :10, 12-Docasadiyndioic acid; C 14 H 17 O 9 N, tetraacetyl-D-xylonic nitrile; C 16 H 32 O 2 , N-hexadecanoic acid; C 17 H 34 O, 2-methylhexadecanal; C 18 H 32 O 2 , 9,12-octadecadienoic acid obtained from P. sajor-caju have been studied by using in silico molecular docking approaches. The results show the selected bioactive molecules have the potential ability to bind with insulin receptor (1GAG) and MHC class 1 protein with different affinity. From the present observations, it can be concluded that these compounds could be novel antidiabetic and antiviral agents.
... Laboratory experiments indicate that many edible and medicinal mushrooms, such as the Ascomycetes and the Basidiomycetes, have antioxidant properties [11,12]. Recent studies have also reported that supplementation of extracts derived from medicinal mushrooms can help boost immune defenses [13], exert a potential antiproliferative effect [14,15], reduce insulin resistance and lipid levels [16,17], show an anticaries action [18], improve mood in patients suffering from major depressive disorder [19], diminish disease-related fatigue [20], and ameliorate cognitive functions in subjects affected by pre-dementia [21]. Some of these therapeutic effects are likely owed to fungal beta-glucans, well known for their immune-modulating and prebiotic effects [22,23]. ...
Edible mushrooms have played a significant role in dietary habits, culinary traditions, folk medicine, myths, and culture since ancient times. This study aims to understand if the regular consumption of edible mushrooms as part of a balanced diet can have some specific beneficial effects on health, especially in preventive medicine. PubMed and Google Scholar were screened for relevant literature reviews, and five articles were included in this work. Overall, mushroom dietary intake was associated with reduced neoplasm incidence, particularly breast cancer, and improved glucose, lipid, and vitamin D levels. However, changes in cholesterol levels were not detected in all studies, and no significant effect was shown for modifications in blood pressure and body weight. In conclusion, the evidence available suggests that a balanced diet including a serving of edible mushrooms at least two-to-three times a week may decrease cancer and metabolic risk in the long run, thus contributing to reducing all-cause mortality risk. The quality of mushrooms and their nutritional characteristics is fundamental to ensure consumer product safety. Further studies should investigate in more depth the effects on health of different mushroom species consumed regularly and the exact minimum amount associated with significant benefits.
... Although there are multiple positive results in vitro and on animals, the available information is still insufficient for a potential use of this mushroom for oncological use, both to define the mechanism of action of its components and its safety and interaction with drugs. Agaricus has also been shown to have antidiabetic effects in vitro and in animal studies [39,40]. Results of a study conducted in human subjects with type 2 diabetes suggest beneficial effects of Agaricus extract in improving insulin resistance [41,42]. ...
... Dietary consumption of Agaricus bisporus reduces diabetes risk factors and can occur over time in adults predisposed to type 2 diabetes (Calvo et al. 2016). The mushroom Agaricus blazei Murill in combination with metformin and gliclazide improved IR among treated subjects with T2DM (Hsu et al. 2007). Supplementation by ganopoly, a polysaccharide fraction extracted from Ganoderma lucidum in patients with T2DM for 12 weeks decreased a glycosylated hemoglobin (HbA1c), FBG, postprandial glucose and increase insulin levels (Gao et al. 2004). ...
... [2] Agaricus blazei a well-known medicinal mushroom used to treat type 2 diabetes as a health promoter in combination with metformin. [36] Ganoderma lucidum, Phellinus linteus, Poria cocos, Inonotus obliquus, Pleurotus ostreatus, Cordyceps sinensis, and Agaricus bisporus are some of the well documented medicinal mushrooms that exhibit significant anti-diabetic properties. [37] In this review, we discuss about the biological nature of different types of diabetes, distinctly explore some favorable mushrooms that have showed clinical and experimental antidiabetic activities and enlightening the correlation of COVID-19 with diabetes. ...
Diabetes is the third most customary non-infectious disease occurring worldwide and leads to untimely disability and mortality. This metabolic disorder is characterized by impaired insulin secretions and high blood glucose levels. Among others, type 2 diabetes is the most common. Various chemical and biochemical hypoglycemic drugs are utilized to control and treat hyperglycemia but required further interventions to reduce their toxicity and side effects on the users. Edible mushrooms have been employed from ancient times to heal many diseases as it composed of anti-oxidant, alkaloids, fibers, triterpenoids, and other phytochemicals. The bioactive secondary metabolites of mushrooms can improve insulin resistance and reduce blood glucose levels by activation of insulin receptor substrate-2, protein kinase B, peroxisome proliferator-activated receptor gamma, and adenosine monophosphate-activated protein kinase pathway. Moreover, mushrooms can inhibit the function of aldolase reductase and α-glucosidase, the two major enzymes responsible for an increased glucose level. Diabetes has increased the chance of viral infections and mortality rates. This article is focused on analyzing the concern of different types of diabetes and summarizing the significance of mushroom as a curative agent. We also discussed the fungal metabolites which acted as a complimentary successor for curing diabetes as it will discursively decrease the severity and mortality rate of patients suffering from outbreak (COVID-19).
... Patients were also given gliclazide and metformin, plus a capsule with 500 mg of A. blazei three times a day. After 12 weeks, patients in this trial showed a significant reduction in insulin resistance, as measured by a drop in HOMAI IR scores [107]. Oral administration of P. ostreatus and P. cystidiosus at a dose of 50 mg/kg/body weight has been shown to increase serum insulin levels and decrease postprandial serum glucose levels in patients with type 2 diabetes [106]. ...
in (Y.K.M.) † These authors contributed equally to this work. Abstract: Diabetes mellitus is a complex illness in which the body does not create enough insulin to control blood glucose levels. Worldwide, this disease is life-threatening and requires low-cost, side-effect-free medicine. Due to adverse effects, many synthetic hypoglycemic medications for diabetes fail. Mushrooms are known to contain natural bioactive components that may be anti-diabetic; thus, scientists are now targeting them. Mushroom extracts, which improve immune function and fight cancer, are becoming more popular. Mushroom-derived functional foods and dietary supplements can delay the onset of potentially fatal diseases and help treat pre-existing conditions, which leads to the successful prevention and treatment of type 2 diabetes, which is restricted to the breakdown of complex polysaccharides by pancreatic-amylase and the suppression of intestinal-glucosidase. Many mushroom species are particularly helpful in lowering blood glucose levels and alleviating diabetes symptoms. Hypoglycaemic effects have been observed in investigations on Agaricussu bru-fescens, Agaricus bisporus, Cordyceps sinensis, Inonotus obliqus, Coprinus comatus, Ganoderma lucidum, Phellinus linteus, Pleurotus spp., Poria cocos, and Sparassis crispa. For diabetics, edible mushrooms are high in protein, vitamins, and minerals and low in fat and cholesterol. The study found that bioac-tive metabolites isolated from mushrooms, such as polysaccharides, proteins, dietary fibers, and many pharmacologically active compounds, as well as solvent extracts of mushrooms with unknown metabolites, have anti-diabetic potential in vivo and in vitro, though few are in clinical trials.
... The supplementation of this mushroom in the diet and drinking water opposed the hyperglycaemia of streptozotocindiabetic mice (Gray & Flatt, 1998). In another trial, it was found that addition of Agaricus blazei extract in amalgamation with metformin and gliclazide for several weeks probably enhanced insulin resistance (IR) in patients suffering from type 2 diabetes (Hsu et al., 2007). ...
Mushrooms have been an indispensable element of the human culture since antiquity and are cherished all over the globe for their nutritive and therapeutic benefits. Being acknowledged as “the new superfood” of the future, they are a cardinal component of human diet for boosting health status and well being. Mushrooms are endowed with antioxidant, antimicrobial, anticancer, prebiotic, antidiabetic, and anti-inflammatory activities, upholding a great therapeutic potential and a huge spectrum of clinical applications. The wide ranges of bioactive compounds including polysaccharides, polysaccharides protein complexes, peptides and proteins, terpenoids and phenolic compounds have been reported from diverse groups of mushroom. Laden with a wealth of nutrients and innumerable biomolecules of therapeutic worth, they are internationally appreciated and envisaged as world's largest untapped resources of dietary supplements. In the recent years, owing to significant healthier lifestyle changes, dietary practices of people and consumers opting for immunity enhancing supplements especially during the COVID-19 pandemic, the yearning for mushroom based nutraceuticals and functional foods is on rise. This review gives comprehensive details on the biodiversity of mushrooms, its nutritional and medicinal importance, secondary metabolites especially of nutraceuticals and pharmaceutical potential, and their role as bioactive agents and application in preparing mushroom based value-added products.
... [23] Hsu et al. reported that low-dose of mushroom agaricus blazei Murill (1500 mg daily) for 12 weeks improves insulin resistance among subjects with T2DM. [24] Although, in their study, the mushroom was intervened in combination with metformin and gliclazide. In a clinical trial, short-term effects of oyster mushroom evaluated in diabetic subjects. ...
Background:
The inflammatory and metabolic responses to mushroom in type 2 diabetes mellitus (T2DM) are unknown. The study aimed to evaluate the effect of Hot Air-dried White Button Mushroom (HAD-WBM) powder on glycemic status, lipid profile, inflammatory markers, and total antioxidant capacity (TAC) in T2DM patients.
Materials and methods:
This randomized controlled trial was conducted at Golestan Hospital, Ahvaz, Iran. Eligible patients were adults aged 20-50 with Type 2 diabetes. Patients were assigned to each group using a randomized block design with block randomization (n = 22, in each group). Randomization was performed by an assistant and group allocation was blinded for the investigator and participants. The intervention and control groups received 16 g/day HAD-WBM or cornstarch powder for 8 weeks. The primary outcomes of interest were fructosamine, fasting blood sugar (FBS), insulin, homeostatic model assessment for insulin resistance, and secondary outcomes were triglyceride, low-density lipoprotein (LDL), high-density lipoprotein, very-LDL, cholesterol, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and TAC.
Results:
After 8 weeks, a significant decrease was observed in fructosamine (-0.228 ± 0.36 vs. 0.03 ± 0.38; P = 0.02) and LDL (-13.05 ± 20.67 vs. 0.81 ± 21.79; P = 0.04) in the HAD-WBM group compared to the control group. No significant changes were observed in fasting insulin and FBS between the two groups. However, a significant within-group reduction (-28.00 ± 42.46; P = 0.006) was observed for FBS in the HAD-WBM group. In the HAD-WBM group, insulin resistance reduced significantly at the end of the study (From 4.92 to 3.81; P = 0.016), but it was not significantly different between the two groups. There was no significant difference in TAC, hs-CRP, and IL-6 between the two groups.
Conclusion:
Considering the results of this study about the beneficial effects of HAD-WBM on the improvement of glycemic indices and LDL in T2DM patients, it is recommended that HAD-WBM could be used to control T2DM.
... • In a random, double-blinded, placebo-controlled experiment including 72 people who has type 2 diabetes who were medicated with prescribed gliclazide and metformin for more than 6 months, the efficacy of A. blazei Murrill in diabetes control was proven (Hsu et al., 2007). The Agaricus blazei mushroom (ABM) extraction was given at a dosage of 1500 mg/d for 12 weeks, and the homeostasis model valuation for insulin resistance (HOMA-IR) were used to examine results. ...
Fungi are extremely diverse in terms of morphology, ecology, metabolism, and phylogeny. Approximately, 130 medicinal activities like antitumor, immunomodulation, antioxidant, radical scavenging, cardioprotective and antiviral actions are assumed to be produced by the various varieties of medicinal mushrooms. The polysaccharides, present in mushrooms like β-glucans, micronutrients, antioxidants like glycoproteins, triterpenoids, flavonoids, and ergosterols can help establish natural resistance against infections and toxins.. Clinical trials have been performed on mushrooms like Agaricus blazei Murrill Kyowa for their anticancer effect, A. blazei Murrill for its antihypertensive and cardioprotective effects, and some other mushrooms had also been evaluated for their neurological effects. The human evaluation dose studies had been also performed and the toxicity dose was evaluated from the literature for number of mushrooms. All the mushrooms were found to be safe at a dose of 2000 mg/kg but some with mild side effects. The safety and therapeutic effectiveness of the fungal mushrooms had shifted the interest of biotechnologists toward fungal nanobiotechnology as the drug delivery system due to the vast advantages of nanotechnology systems. In complement to the vital nutritional significance of medicinal mushrooms, numerous species have been identified as sources of bioactive chemicals. Moreover, there are unanswered queries regarding its safety, efficacy, critical issues that affect the future mushroom medicine development, that could jeopardize its usage in the twenty-first century.
... In a randomized, double-blind, placebocontrolled clinical study, Hsu et al., (2007) evaluated the effect of metformin and gliclazide combined with ABM extract. Seventy-two patients participated in the study, aged between 20 and 75 years old, type 2 diabetics [126]. Among the parameters evaluated at the beginning and the end of treatment were fasting blood glucose, HbA 1C , insulin, adiponectin and homeostasis model assessment of insulin resistance (HOMA-IR). ...
Edible mushrooms have been increasingly introduced into the human diet, which has driven research into their functional properties. Thus, Agaricus brasiliensis Murill or Agaricus blazei Murill (ABM) is a species native to the Brazilian biome, whose fruitful body has been used not only for dietary purposes, but also in the development of functional foods or as source of molecules of pharmacological interest. The bioactivity of ABM has been related to the presence of polysaccharides, although the contribution of others metabolites cannot be discharged. This work describes the polysaccharides isolation methodology and preparation of the extracts of ABM and their biological activities. Furthermore, it presents a general outline of its characterizations regarding composition, chemical structure and properties in solution. The ABM and its chemical constituents exhibit several biological activities that support their potential use for prevention or treatment of diseases with inflammatory background, such as cancer, diabetes and atherosclerosis. The mechanism of action of the extracts and polysaccharides from ABM is mainly related to a modulation of immune system response or reduction of inflammatory response. This review shows that the ABM has great potential in the pharmaceutical, biotechnological and food sectors that deserves additional research using standardized products.
... These phytochemicals possess a significant hypoglycemic effect. Our findings agreed with Hsu et al. [98]. A. bracteosa possessed antioxidant activities that can reduce the diabetic effect. ...
Background:
Ajuga bracteosa is a traditional herb used against various diseases.
Objective:
Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu).
Methods:
In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration.
Results:
In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepato-protective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared to Glibenclamide treated group. Significant reduction in ALT, AST, ALP, urea, uric acid, and creatinine was recorded in ABaqu and ABAgNPs treated diabetic mice. The hepato-protective findings indicated that ALT, ALP, AST were elevated in CCl4-induced mice while declined in both ABAgNPs and ABaqu treated CCl4-induced mice. Histopathological examination revealed that ABAgNPs have hepato-protective activity.
Conclusion:
It was concluded that ABAgNPs and ABaqu possessed strong anti-diabetic and hepato-protective phytoconstituents which could be used in the prevention of diseases.
... Improves insulin resistance. 12 Concern for hypoglycemia in combination with other medications. ...
The widespread use of complementary products poses a challenge to clinicians in the perioperative period and may increase perioperative risk. Because dietary supplements are regulated differently from traditional pharmaceuticals and guidance is often lacking, the Society for Perioperative Assessment and Quality Improvement convened a group of experts to review available literature and create a set of consensus recommendations for the perioperative management of these supplements. Using a modified Delphi method, the authors developed recommendations for perioperative management of 83 dietary supplements. We have made our recommendations to discontinue or continue a dietary supplement based on the principle that without a demonstrated benefit, or with a demonstrated lack of harm, there is little downside in temporarily discontinuing an herbal supplement before surgery. Discussion with patients in the preoperative visit is a crucial time to educate patients as well as gather vital information. Patients should be specifically asked about use of dietary supplements and cannabinoids, as many will not volunteer this information. The preoperative clinic visit provides the best opportunity to educate patients about the perioperative management of various supplements as this visit is typically scheduled at least 2 weeks before the planned procedure.
... Currently, in contrast to the high number of experimental results, there is a very limited number of clinical trials of several mushroom species that are used as drugs for patients with type 2 diabetes. In a randomized, double-blind, placebo-controlled clinical trial, the mushroom Agaricus Blazei Murill in combination with metformin and gliclazide improved insulin resistance among treated subjects with type 2 diabetes when compared with the placebo group [93]. Other human clinical studies aiming to evaluate the efficacy and safety G. lucidum in patients with confirmed type 2 diabetes with intervention lengths of 4-12 weeks have reported improvements in glycosylated haemoglobin (HbA1c), fasting plasma glucose, postprandial glucose, insulin, and C-peptide [94], whilst other studies have reported no changes in glucose parameters [95,96]. ...
Diabetes mellitus is a life-threatening multifactorial metabolic disorder characterized by high level of glucose in the blood. Diabetes and its chronic complications have a significant impact on human life, health systems, and countries’ economies. Currently, there are many commercial hypoglycemic drugs that are effective in controlling hyperglycemia but with several serious side-effects and without a sufficient capacity to significantly alter the course of diabetic complications. Over many centuries mushrooms and their bioactive compounds have been used in the treatment of diabetes mellitus, especially polysaccharides and terpenoids derived from various mushroom species. This review summarizes the effects of these main mushroom secondary metabolites on diabetes and underlying molecular mechanisms responsible for lowering blood glucose. In vivo and in vitro data revealed that treatment with mushroom polysaccharides displayed an anti-hyperglycemic effect by inhibiting glucose absorption efficacy, enhancing pancreatic β-cell mass, and increasing insulin-signaling pathways. Mushroom terpenoids act as inhibitors of α-glucosidase and as insulin sensitizers through activation of PPARγ in order to reduce hyperglycemia in animal models of diabetes. In conclusion, mushroom polysaccharides and terpenoids can effectively ameliorate hyperglycemia by various mechanisms and can be used as supportive candidates for prevention and control of diabetes in the future.
... The efficacy of A. blazei Murrill in diabetes control was also demonstrated in a randomized, double-blind, placebo-controlled trial involving 72 individuals with type 2 diabetes treated with gliclazide and metformin for more than 6 months [98]. The Agaricus blazei mushroom(ABM) extract was administered for 12 weeks at a dose of 1500 mg/d and then the homeostasis model assessment for insulin resistance (HOMA-IR) was evaluated. ...
Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms.
... Its effect in reducing insulin resistance was found via an increasing level of adiponectin. Clinically, its aqueous extract at 500 mg trice a day plus conventional antidiabetic drugs produced a significant decrease in glucose level of T2DM patients when F I G U R E 2 Antidiabetic activity of ginseng and berberine via different pathways compared to control group (Hsu, Liao, Lin, Hwang, & Chou, 2007). ...
Diabetes mellitus is a growing public health concern and an increasing interest has been raised to search for new compounds with therapeutic effects on β-cells. There are chronic insulin resistance and loss of β-cell mass in the case of type-2 diabetes which covers about 90% of total diabetic patients. This work aims to critically review the protective and regenerative effects of various antidiabetic natural products on pancreatic β-cells. A thorough literature survey was conducted on the natural molecules and extracts having a protective, regenerative, and repairing effect on β-cells. The primary source of the literature was online scientific databases such as PubMed, Scopus, and Google Scholar. Besides, selected relevant textbooks were also consulted. Various natural molecules including berberine, curcumin, mangiferin, stevioside and capsaicin, and extracts obtained from the plants like Capsicum annum, Gymnema sylvestre, Stevia rebaudiana and Nymphaea stellate, were found to produce regenerative and anti-apoptosis effects on β-cells. These natural products were also found to increase insulin secretion by stimulating β-cells. The present review concluded that a large number of molecules and extracts, abundantly found in nature, possess antidiabetic effect via targeting β-cells. Further research is warranted to use these agents as a drug against diabetes.
... A comparative study revealed that ethyl acetate extracts of P. osteratus exerted hypoglycemic activity in mice with alloxaninduced diabetes [120]. The edible mushroom A. blazei Murill has been used as a health promoter in combination with metformin and gliclazide to improve the cell response to insulin in T2DM [121]. Agaricus blazei Murill (ABM), a medicinal mushroom, has beneficial effects on various human metabolic diseases. ...
Metabolic syndrome is an aggregation of conditions and associated with an increased risk of developing diabetes, obesity and cardiovascular diseases (CVD). Edible mushrooms are widely consumed in many countries and are valuable components of the diet because of their attractive taste, aroma, and nutritional value. Medicinal mushrooms are higher fungi with additional nutraceutical attributes having low fat content and a trans-isomer of unsaturated fatty acids along with high fiber content, biologically active compounds such as polysaccharides or polysaccharide β-glucans, alkaloids, steroids, polyphenols and terpenoids. In vitro experiments, animal models, and even human studies have demonstrated not only fresh edible mushroom but also mushroom extract has great therapeutic applications in human health as they possess many properties such as anti-obesity, cardioprotective and anti-diabetic effect. They are considered as the unmatched source of healthy foods and drugs. The focus of this report was to provide a concise and complete review of the novel medicinal properties of fresh or dry mushroom and extracts, fruiting body or mycelium and its extracts, fiber, polysaccharides, beta- glucan, triterpenes, fucoidan, ergothioneine from edible mushrooms that may help to prevent or treat metabolic syndrome and associate diseases.
... Others have failed to produce decreases in HbA1C of 0.5% or more in less than 3 months. These include Agaricus blazei [197], American ginseng (Panax quinquefolius L.) [198], pomegranate extract [199], green tea [200], cinnamon [201], flaxseed oil [202], French maritime pine bark [203], ginseng [121], Juglans regia extract [204], Liuwei Dihuang pills [205], bitter melon (Momordica charantia) [206][207], rosehip (Rosa canina L). [208], Salvia officinalis [209], Soy phytoestrogens [210], Tinospora cordifolia [211], Tinospora crispa [212], Hibiscus Sabdariffa [153], Citrus aurantium [213], sea buckthorn [214], bilberries [215], Ilex paraguariensis [216], Phaseolus vulgaris and Ceratonia siliqua combinations [217], grape seeds and pine bark [218], Ipomoea batatas and Silybum marianum [165]. ...
At present, the pathologic spectrum of obesity-insulin resistance (IR)-diabetes mellitus (DM) represents not only a pressing matter in public health but also a paramount object of study in biomedical research, as they constitute major risk factors for cardiovascular disease (CVD), and other chronic non-communicable diseases (NCD). Phytotherapy, the use of medicinal herbs (MH) with treatment purposes, offers a wide array of opportunities for innovation in the management of these disorders; mainly as pharmacological research on small molecules accumulates. Several MH have displayed varied mechanisms of action relevant to the pathogenesis of obesity, IR and DM, including immunological and endocrine modulation, reduction of inflammation and oxidative stress (OS), regulation of appetite, thermogenesis and energy homeostasis, sensitisation to insulin function and potentiation of insulin release, among many others. However, the clinical correlates of these molecular phenomena remain relatively uncertain, with only a handful of MH boasting convincing clinical evidence in this regard. This review comprises an exploration of currently available preclinical and clinical research on the role of MH in the management of obesity, IR, and DM.
... Mejora la resistencia insulínica de forma potencial, ya que tras tomar dicho extracto durante 12 semanas se produjo un aumento de la concentración de adiponectina (in vivo). Hsu et al., (2007) Jeong et al., (2010 ...
Higher fungi or mushrooms have been harvested and consumed by humans for thousands of years due to their nutritional and medicinal qualities. Currently, mushrooms are consumed all over the world for their excellent flavour and texture, although there is little known about their great potential as a functional food. For this reason, the main objective of this work was to identify the functional properties of wild and cultivated mushrooms and their bioactive or pharmacological characteristics that justify their use as functional foods. The information was obtained from various databases such as PubMed, Google Scholar, Web of Science and Scielo, among others, as well as external books. It was found that there are plenty of edible mushrooms containing compounds such as β-glucans or polysaccharide-protein complexes which are responsible for functional activities such as antitumour, immunomodulatory, antioxidant, antimicrobial, etc. Eighty two scientific articles were reviewed and it was concluded that only 4 fungi have most of the functional properties described above. Two of them belong to the genus Agaricus, Agaricus bisporus and Agaricus blazei (mushrooms) and the other two are Ganoderma lucidum (Reishi) and Lentinula edodes (Shiitake). RESUMEN Los hongos superiores o setas han sido recolectados y consumidos por el ser humano durante miles de años, tanto por sus cualidades nutritivas como medicinales. Actualmente, los hongos son consumidos en todo el mundo por su excelente sabor, aroma y textura, aunque es poco conocido su gran potencial como alimentos con propiedades funcionales. Por ello, el objetivo principal de este trabajo ha sido realizar una revisión bibliográfica para identificar los géneros y especies de hongos silvestres y cultivados con propiedades funcionales, así como los compuestos bioactivos o farmacológicos responsables de dichas propiedades. Para ello, se ha obtenido información de diversas bases de datos como PubMed, Google Académico, Web of Science o Scielo, entre otras. También se han realizado consultas de libros externos. Tras la revisión bibliográfica de este trabajo hemos identificado gran cantidad de géneros y especies de hongos que contienen compuestos bioactivos como los β-glucanos o complejos polisacárido-proteína, responsables de las actividades funcionales. Caben destacar entre otras las propiedades antitumorales, inmunomoduladoras, antioxidantes y antimicrobianas. De los 82 artículos científicos revisados, podemos concluir que únicamente 4 hongos presentan la mayoría de las propiedades funcionales descritas. Dos de estos hongos pertenecen al género Agaricus, el Agaricus bisporus y el Agaricus blazei (Champiñones) y los otros dos son el Ganoderma lucidum (Reishi) y la Lentinula edodes (Shiitake)". Palabras clave: compuestos bioactivos, propiedades antitumorales, inmunomoduladoras, antioxidantes. CIENCIA DE LOS ALIMENTOS INTRODUCCIÓN Los hongos superiores o setas han atraído al ser humano durante siglos. La palabra hongo tiene su ori-gen en el término latino "fungus", que proviene de la combinación de los vocablos funnus (cadáver) y ago (hacer). Literalmente significa "hacer cadáver" (Ca-longe, 1990). Si los antiguos romanos relacionaban los hongos con la muerte a causa del fallecimiento por envenenamiento del emperador Claudio, para los griegos eran símbolo de vida (Hernando, 2005). En los últimos años ha aumentado considerablemente el cul-tivo y consumo de hongos a nivel mundial, y se prevé que la tendencia siga una línea ascendente. En 2015 la demanda mundial para el mercado de hongos fue valorada en más de 35,08 mil millones de dólares y se espera que llegue a los 59,48 mil millones de dólares en 2021. Además, se prevé su crecimiento a una tasa compuesta anual ligeramente por encima de 9,2%, en-tre 2016 y 2021 (Agrimundo, 2016). La industria de los
... There is a growing body of evidence that suggests consuming several mushroom species, either as a food or as extracts, may improve physical and mental health [5,6]. Mushrooms are rich in bioactive compounds, particularly ergothioneine, ergosterol, vitamin D, beta-glucan and selenium, and these bioactive compounds have been favourably linked to immune function [7,8], glycaemic control [9,10], weight management [11], lipid profile [12,13], blood pressure [14], bone density [15], gut health [16], cancer [17,18] and cognitive function [19]. These health benefits are thought to be largely a result of the enhancement of cellular immunity to produce immunomodulatory, anti-carcinogenic, antimicrobial and hypocholesterolemic effects [5], and due to their effects on the gastrointestinal microbiota (19). ...
There is evidence from both in vitro and animal models that the consumption of edible mushrooms has beneficial effects on health. It is unclear whether similar effects exist in humans and which bioactive compounds are present. This review synthesises the evidence on the world's most commonly consumed mushroom, Agaricus bisporus to (i) examine its effect on human health outcomes; and (ii) determine the nutrient density of its bioactive compounds, which may explain their health effects. A systematic literature search was conducted on the consumption of A. bisporus, without date and study design limits. Bioactive compounds included ergosterol, ergothioneine, flavonoids, glucans and chitin. Two authors independently identified studies for inclusion and assessed methodological quality. Beneficial effects of A. bisporus on metabolic syndrome, immune function, gastrointestinal health and cancer, with the strongest evidence for the improvement in Vitamin D status in humans, were found. Ultraviolet B (UVB) exposed mushrooms may increase and maintain serum 25(OH)D levels to a similar degree as vitamin D supplements. A. bisporus contain beta-glucans, ergosterol, ergothioneine, vitamin D and an antioxidant compound usually reported as flavonoids; with varying concentrations depending on the type of mushroom, cooking method and duration, and UVB exposure. Further research is required to fully elucidate the bioactive compounds in mushrooms using vigorous analytical methods and expand the immunological markers being tested. To enable findings to be adopted into clinical practice and public health initiatives, replication of existing studies in different population groups is required to confirm the impact of A. bisporus on human health.
... A randomized, double-blinded, and placebo-controlled clinical trial (n = 72) showed that A. blazei Murill supplementation in combination with metformin and gliclazide improved insulin resistance in these subjects. An increase in adiponectin concentration after A. blazei extract consumption for 12 weeks may be the relevant mechanism (Hsu et al. 2007). Jayasuriya et al. (2012) reported that long-term consumption of P. ostreatus and P. cystidiosus as a functional food appears to be effective for glycemic control. ...
Mushrooms are becoming a vital component of the human diet for the prevention and treatment of various diseases. The use of mushrooms for developing functional foods, drugs, and nutraceuticals is reviewed in this chapter, with emphasis on present or potential medical implications. As functional foods, mushrooms represent a paradigm of integrating tradition and novelty, due to their wide spectrum of pharmacological properties. Their bioactive components can be extracted or concentrated as nutraceuticals, and/or a diverse class of dietary supplements. Functional foods and nutraceuticals, particularly mushrooms, are immunoceuticals with antitumor and immunomodulatory effects which target and modulate biological processes that foster the development of diseases. Several mushroom products, mainly polysaccharides such as β‐D‐glucans, have proceeded successfully through clinical trials and are used as drugs to treat cancer and chronic diseases. In sum, the present status and future prospects open new avenues for upgrading mushroom species from functional food to translational mushroom medicine.
... 33 In addition, studies using normal and diabetic animals demonstrated that the hypoglycemic effects of polysaccharides extracted from Agaricus blazei Murill are due to direct interactions between its β-glucans and the insulin receptors in target tissues. 34 In view of these results, we speculated that the antihyperglycemic activity of ARPs-p can be attributed to its high glucose content and β-configuration structure. Remarkably, the hepatic glycogen and blood glucose levels were almost normalized in groups VI and III to nearly the same degree, while the serum insulin levels in group VI were still lower than those of the control mice (group I) and glibenclamide-treated mice (group III) (P < 0.05). ...
Anoectochilus roxburghii, a traditional Chinese medicinal herb, has been widely used for treating numerous chronic diseases. In this study, a polysaccharide from A. roxburghii (ARPs-p) was purified by anion exchange and size exclusion chromatography. The structural characteristics of ARPs-p were systematically investigated for the first time via numerous chromatographic techniques, periodic acid oxidation, Smith degradation, methylation analysis, FTIR spectroscopy and 1D/2D NMR spectroscopy. The results showed that ARPs-p is a heteropolysaccharide with a molecular weight of 97 kDa; it consists of 97.75% glucose, 1.2% galactose and trace amounts of galacturonic acid, and its backbone structure is composed of →3)-β-D-Glcp-(1→ with some branching points at O-6 linked to non-reducing end units or 6-O-linked Glcp units. Furthermore, streptozotocin (STZ)-induced diabetic mouse experiments suggested that ARPs-p has excellent antihyperglycemic, antioxidant and antihyperlipidemic activities, in which 1,3-β-D-glucan, the main component of ARPs-p, plays a vital role.
... Mushrooms, as functional foods, might have a particularly high potential impact for the prevention of diabetes, as well as curative properties for the condition more than other species (Perera and Li, 2011). A randomized placebo control study by Hsu et al. (2007) showed that 12 weeks of treatment with mushroom extract improved insulin resistance in patients, 20 to 75 years of age, who had had type 2 diabetes for more than one year. This beneficial effect of mushroom could be attributed to adiponectin concentration found in mushrooms; its consumption among people with high risk should be encouraged for prevention. ...
The management of diabetes is crucial since that is the only option for this chronic non-communicable disease. The administration of medicinal drugs for the management of diabetes is critical. It is however important to note that some plants have components that confer anti-diabetic properties and may be of use especially in developing countries where there is limited access to healthcare. The aim of this review is to review studies that involved plants with anti-diabetic effects. Such plants as tea, mushroom, broccoli, garlic, moringa, ginseng, guava, onion, tiger nut, bush mango, okra, dates, bitter melon, dandelion, watermelon, and pumpkins may reduce diabetes risks, or even lower blood glucose in diabetes patients (notably type 2 diabetes). Phytoremediation via plant foods should not be underestimated in the management of diabetes.
... Inflammation and oxidative stress contribute to lifestyle-related diseases, such as obesity and diabetes. Multiple studies have demonstrated that AGA can ameliorate the symptoms of lifestyle-related diseases [6][7][8], including obesity [9,10], hypertension [11], and diabetes [12,13]. Furthermore, it has been shown that AGA has anti-tumor [14,15], cancer suppression [16][17][18], and immune-enhancing properties [19][20][21][22][23][24][25]. ...
Non-alcoholic steatohepatitis (NASH) is a progressive disease that occurs in the liver. As the number of people with NASH has increased, effective prevention and treatment strategies are needed. Agaricus brasiliensis KA21 (AGA) is a mushroom native to Brazil and is considered a healthy food because of its purported health benefits, including its antioxidant properties. In this study, we focused on the oxidative stress that accompanies the onset of NASH and examined whether AGA can prevent NASH development through its antioxidant activity. We used a mouse model of NASH in which pathogenesis was promoted by dietary induction. Supplementation with AGA attenuated the development of hepatic fibrosis, which is a characteristic feature of late-stage NASH. This effect appeared to be mechanistically linked to an AGA-promoted reduction in hepatic oxidative stress. These results demonstrate a novel role for AGA in NASH prevention.
... Altı çalışmada, bitkisel ürünlerin fructus mume formüle, (35) yeşil çay, (19) PURIAM110 (acı turunç ve dut yaprağı), (36) yeşil çay ve ebegümeci çayı, (26) tarçın ve Kafkas dağ mersininin, (21) FPG ve HbA1c'de önemli düzeyde düşmeye neden olduğu görülmesine rağmen, plasebo grubu ile karşılaştırıldığında bunun anlamlı olmadığı belirlenmiştir. Beş çalışmada kullanılan bitkisel ürünlerin; yeşil çay ve ebegümeci çayı, (26) zencefil, (34) TM81 (Çin bitkisel karışımı), (33) resveretrol, (30) agaricus blazei mantar özü, (37) HOMA-IR indeksini düşürmede önemli düzeyde etkili olduğu bulunmuştur. ...
Although the living standard and life expectancy have been increasing significantly, we face numerous arising challenges in modern medicine, such as the presence of increasing exogenous triggers of oxidative stress that lead to the emergence of multiple diseases and disorders, the appearance of an increasing number of resistant microorganisms, an immense number of patients suffering from cardiovascular diseases, cancers, diabetes, neurodegenerative disorders as well as autoimmune and rare diseases. Therefore, we need the help of natural sources of active compounds, among which mushrooms are important. They have been an integral part of traditional medicine for centuries, and modern research has confirmed their bioactivities and given them a scientific basis. Numerous species, primarily from the genera Ganoderma, Lentinus, Pleurotus, Innonotus, Trametes, Cordyceps, Agaricus, etc., have shown exceptional immunomodulatory, antioxidative, antihypercholesterolemic, antihypertensive, antitumor, antineurodegenerative, antidiabetic, antimicrobial as well as numerous other potentials. Studies have shown that the mushrooms’ crude extracts, as well as various metabolites, especially polysaccharides, phenolic compounds, terpenoids, and proteins, possess mentioned activities and thereby could be the basis for the development of new, more efficient drugs. However, numerous problems and challenges need to be overcome before mushrooms from the domain of traditional medicine move into the modern one and become part of conventional therapy.KeywordsBioactivitiesDrug developmentFunctional foodMedicinal mushroomsTraditional medicine
The human uses of mushrooms and cultured mycelium products for nutrition and medicine are detailed and supported by available human studies, which in many cases are clinical trials published in peer-reviewed journals. The major medically active immunomodulating compounds in the cell walls-chitin, beta-glucans, and glycoproteins, as well as lower weight molecules-nitrogen-containing compounds, phenolics, and terpenes-are discussed in relation to their current clinical uses. The nutritional content and foods derived from mushrooms, particularly related to their medical benefits, are discussed. High-quality major nutrients such as the high amounts of complete protein and prebiotic fibers found in edible and medicinal fungi and their products are presented. Mushrooms contain the highest amount of valuable medicinal fiber, while dried fruiting bodies of some fungi have up to 80% prebiotic fiber. These fibers are particularly complex and are not broken down in the upper gut, so they can diversify the microbiome and increase the most beneficial species, leading to better immune regulation and increasing normalizing levels of crucial neurotransmitters like serotonin and dopamine. Since the growth of medicinal mushroom products is expanding rapidly worldwide, attention is placed on reviewing important aspects of mushroom and mycelium cultivation and quality issues relating to adulteration, substitution, and purity and for maximizing medicinal potency. Common questions surrounding medicinal mushroom products in the marketplace, particularly the healing potential of fungal mycelium compared with fruiting bodies, extraction methods, and the use of fillers in products, are all explored, and many points are supported by the literature.
Since ancient times, mushrooms have been a valuable food source and traditional medicine worldwide. Edible mushrooms possess high nutritional value and medicinal significance due to the presence of a large number of active ingredients that cause the development of therapeutic functions. They are used to treat severe diseases like microbial and viral infections, cancer, tumors, inflammation, and cardiovascular and immune diseases. Mushrooms contain various bioactive compounds, including α- and ß-glucans, proteoglycan, lectin, phenolic compounds (flavonoids, flavonoids, phenolic acids), polysaccharides, triterpenoids, steroids, lentinan, schizophyllan, lovastatin, pleuran, glycopeptides, alkaloids, dietary fiber, and others. The biological activities of some well-known edible mushrooms are discussed in this chapter.KeywordsAnticancerBiological activityEdible mushroomsMacrofungusPolysaccharides
Cancer progression and mortality remain challenging because of current obstacles and limitations in cancer treatment. Continuous efforts are being made to explore complementary and alternative approaches to alleviate the suffering of cancer patients. Epidemiological and nutritional studies have indicated that consuming botanical foods is linked to a lower risk of cancer incidence and/or improved cancer prognosis after diagnosis. From these observations, a variety of preclinical and clinical studies have been carried out to evaluate the potential of botanical food products as anticancer medicines. Unfortunately, many investigations have been poorly designed, and encouraging preclinical results have not been translated into clinical success. Botanical products contain a wide variety of chemicals, making them more difficult to study than traditional drugs. In this review, with the consideration of the regulatory framework of the USFDA, we share our collective experiences and lessons learned from 20 years of defining anticancer foods, focusing on the critical aspects of preclinical studies that are required for an IND application, as well as the checkpoints needed for early-phase clinical trials. We recommend a developmental pipeline that is based on mechanisms and clinical considerations.
For millennia, edible mushrooms have been used as a common diet for mankind based on their nutritional importance and medicinal benefits. Edible mushrooms are a rich source of carbohydrates (sucrose, xylose, rhamnose, mannose, and fructose), amino acids (glutamic acid, aspartic acid, glutamate, methionine, and cysteine), proteins, fatty acids (linoleic acid, stearic acid, palmitic acid, adrenic acid, and nervonic acid), vitamins (folate, riboflavin, ascorbic acid niacin, thiamine, ergocalciferol, and cyanocobalamine) mineral contents (Ca, Mg, K, P, Na, Fe, Cu, Zn, Cd, and Mo) and phenolic compounds (gallic acid, caffeic acid, protocatechuic acid, p-coumaric acid, p-hydroxybenzoic acid and pyrogallol) that control and ameliorate multiple functions of the human body and participate for maintaining the good health by reducing the occurrence of several chronic diseases. Bioactive polysaccharides, peptides, polyphenols, and dietary fibers extracted from mushroom mycelia have health-promoting properties including a number of medicinal benefits such as anticancerous properties, antihypertensive activity, protection against DNA damage, cardiovascular effects, neurodegenerative disorders, and improvement in innate immunity. In developing countries, the utilization of mushrooms for therapeutic applications is being implemented as a boon for promoting human health and natural dietary supplements. Recently, different pharmaceutical companies and food industries have taken initial steps for patenting the medicinal value of edible mushrooms based on their antioxidant, anticancer, hypolipidemic, hypotensive, and immunomodulatory effects. The immense role of nutritional components and bioactive molecules of edible mushrooms in correlation with health problems has become a burning task in modern nutraceutical therapy. Hence, the present article deals with up-to-date knowledge of edible mushrooms as a nutritional adjuvant with emphasis on profound biological properties and potential mechanisms of action to prevent different health diseases.
Numerous mushroom bioactive metabolites, including polysaccharides, eritadenine, lignin, chitosan, mevinolin, and astrakurkurone have been studied in life-threatening conditions and diseases such as diabetes, cardiovascular, hypertension, cancer, DNA damage, hypercholesterolemia, and obesity attempting to identify natural therapies. These bioactive metabolites have shown potential as antiviral and immune system strengthener natural agents through diverse cellular and physiological pathways modulation with no toxicity evidence, widely available, and inexpensive. In light of the emerging literature, this paper compiles the most recent information describing the molecular mechanisms that underlie the nutraceutical potentials of these mushroom metabolites suggesting their effectiveness if combined with existing drug therapies while discussing the food functionality of mushrooms. The findings raise hope that these mushroom bioactive metabolites may be utilized as natural therapies considering their therapeutic potential while anticipating further research designing clinical trials and developing new drug therapies while encouraging their consumption as a natural adjuvant in preventing and controlling life-threatening conditions and diseases.
Practical applications
Diabetes, cardiovascular, hypertension, cancer, DNA damage, hypercholesterolemia, and obesity are among the world's largest life-threatening conditions and diseases. Several mushroom bioactive compounds, including polysaccharides, eritadenine, lignin, chitosan, mevinolin, and astrakurkurone have been found potential in tackling these diseases through diverse cellular and physiological pathways modulation with no toxicity evidence, suggesting their use as nutraceutical foods in preventing and controlling these life-threatening conditions and diseases.
The plasticity of the gut microbiota (GM) creates an opportunity to reshape the biological output of gut microbes by manipulating external factors. It is well known that edible fungal polysaccharides (EFPs) can reach the distal intestine and be assimilated to reshape the GM. The GM has unique devices that utilize various EFPs and produce oligosaccharides, which can selectively promote the growth of beneficial bacteria and are fermented into short-chain fatty acids that interact closely with intestinal cells. Here we review EFPs-based interventions for the GM, particularly the key microorganisms, functions, and metabolites. In addition, we discuss the bi-directional causality between GM imbalance and diseases, and the beneficial effects of EFPs on host health via GM. This review can offer a valuable reference for the design of edible fungal polysaccharide- or oligosaccharide-based nutrition interventions or drug development for maintaining human health by targeted regulation of the GM.
Selenoproteins in selenium (Se)-enriched vegetables play an important role in human health. In this study, three water-soluble selenoproteins PR-Se-1, PR-Se-2 and PR-Se-3 in Agaricus blazei Murrill (ABM) were isolated by anion exchange chromatography, gel filtration chromatography and SDS-PAGE. Sequence analyses performed by HPLC–MS/MS showed that PR-Se-1, a 114024 Da selenoprotein with 1019 amino acids (AAs), is an isoenzyme of isocitrate dehydrogenase. PR-Se-2, a 53983 Da selenoprotein with 508 AAs, is a kind of dihydrolipoyl dehydrogenase. PR-Se-3, a 47179 Da selenoprotein with 415 AAs, is a kind d-proline reductase. Se content is high at 26.1 μg/g, and selenocystine is the predominant Se unit in the three selenoproteins. Se content of ABM is 9.15 μg/g, and the organic form of Se accounts for ~81% of total Se content. ABM could be a promising source of Se in Se-poor regions.
Several medicinal mushrooms exhibit hypoglycaemic activities in vitro and in animal studies. In contrast to the high number of experimental results, only a few clinical trials and/or case reports have been published. They exist for mushrooms of the genera Agaricus, Coprinus, Ganoderma, Grifola, and Pleurotus. This article critically reviews these clinical investigations and describes which tasks need to be done to explore the potential of mushrooms for supportive treatment of type 2 diabetes.
Several medicinal mushrooms exhibit hypoglycaemic activities in vitro and in animal studies. In contrast to the high number of experimental results, only a few clinical trials and/or case reports have been published. They exist for mushrooms of the genera Agaricus, Coprinus, Ganoderma, Grifola, and Pleurotus. This article critically reviews these clinical investigations and describes which tasks need to be done to explore the potential of mushrooms for supportive treatment of type 2 diabetes.
Diabetes mellitus is a metabolic disorder due to increased level of glucose in blood that affects millions of individuals. If not managed properly, it can lead to life threatening complications, organ failure and mortality. Research has recognized that diabetes can be prevented and managed by following proper lifestyle which includes diet and exercise. Though a number of synthetic drugs are available for managing this condition, their long-term use is associated with many side effects. This has shifted the research towards medicinal plants and herbs which are considered to be comparatively safe. Edible mushrooms belong to the class of potential anti-diabetic phytotherapy. They are rich in natural compounds such as fibers, polysaccharides, phenolics and alkaloids and known for providing antidiabetic, antioxidant and antihyperlipidemic effects from ancient times. Moreover, mushroom polysaccharides also act as prebiotics and modulate the composition of gut microflora; and thus, can reduce insulin resistance. The present review discusses the pathophysiology of diabetes and, elaborates some potential mushroom species that are known to have antihyperglycemic activities. Different mushroom polysaccharides modulating the composition of gut microflora in diabetic animal models have also been discussed.
Diabetes remains the major public health challenge to 21st century. It is strongly related to lifestyle changes. Most chronic complications of diabetes are macrovascular and microvascular diseases resulting from the existing hyperglycemic status. Failure of first line therapy which is based on diet modifications and exercise, conventional treatment using antihyperglycemic agents with different mechanisms of action will be implemented for type II diabetes in modern medicine. Higher Basidiomycetes mushrooms are highly praised for their nutritional value and pharmacological properties. They have long been used traditionally for the maintenance of health, prevention and treatment of various human ailments. Reports indicate the beneficial effects of medicinal mushrooms in diabetes treatments. However, scientific evidences are insufficient to make definitive conclusions on the efficacy of individual medicinal mushrooms. Mushrooms belong to the genera Phellinus such as Phellinus linteus, Phellinus ribis, Phellinus rimosus and Phellinus igniarius. They possess significant hypoglycemic effect in experimental diabetic models. However, well-designed controlled clinical trials are needed to establish their safety and bioactivity.
Animal studies have suggested that mushroom intake can alleviate non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory and antioxidant properties. However, the association between mushroom intake and NAFLD is unknown in humans. We aimed to investigate the association of mushroom intake with NAFLD among Chinese adults. This is a cross-sectional study of 24,236 adults (mean [standard deviation] age: 40.7 [11.9] years; 11,394 men [47.0%]). Mushroom intake was assessed via a validated food frequency questionnaire. Newly diagnosed NAFLD was identified based on the results of annual health examinations, including ultrasound findings and a self-reported history of the disease. Multiple logistic models were used to examine the association between mushroom intake and NAFLD. The prevalence of newly diagnosed NAFLD was 19.0%. Compared to those consuming mushrooms less frequently (≤1 time/week), the fully adjusted odds ratios (95% confidence intervals) of newly diagnosed NAFLD were 0.95 (0.86, 1.05) for those consuming 2-3 times/week and 0.76 (0.63, 0.92) for those consuming ≥4 times/week, respectively ( P for trend = 0.01). The inverse association was consistent in subgroups defined by age, sex, and body mass index. In conclusion, higher mushroom intake was significantly associated with lower prevalence of NAFLD among Chinese adults. Future research is required to understand the causal association between mushroom intake and NAFLD.
Troglitazone decreases insulin resistance and hyperglycemia in patients with non-insulin-dependent diabetes mellitus (NIDDM), but its effects on subjects without diabetes are not known.
We performed oral and intravenous glucose-tolerance tests, studies with the euglycemic-hyperinsulinemic clamp, meal-tolerance tests, and 24-hour blood-pressure measurements at base line and after the administration of troglitazone, 200 mg orally twice daily, or placebo for 12 weeks in 18 nondiabetic obese subjects, 9 of whom had impaired glucose tolerance.
The mean (+/- SD) rates of glucose disposal increased from 4.7 +/- 1.7 to 6.0 +/- 1.7 mg per kilogram of body weight per minute (P = 0.004) and from 9.0 +/- 1.8 to 9.9 +/- 1.3 mg per kilogram per minute (P = 0.02) during insulin infusions of 40 and 300 mU per square meter of body-surface area per minute, respectively, in the troglitazone group. The insulin-sensitivity index, calculated from the results of intravenous glucose-tolerance tests, increased from 0.7 +/- 0.6 x 10(-4) to 1.6 +/- 0.9 x 10(-4) in subjects given troglitazone, and their glycemic response to oral glucose and to mixed meals decreased. The mean fasting plasma insulin concentration decreased by 48 percent (P = 0.002), and the plasma insulin response to oral glucose and mixed meals decreased by 40 and 41 percent, respectively. The changes were similar in the subjects with normal glucose tolerance and those with impaired glucose tolerance. Systolic and diastolic blood pressure decreased by 5 +/- 2 mm Hg (P = 0.05) and 4 +/- 2 mm Hg (P = 0.04), respectively, after treatment with troglitazone. There were virtually no changes in the placebo group.
Troglitazone decreases insulin resistance and improves glucose tolerance in obese subjects with either impaired or normal glucose tolerance. The ability of troglitazone to reduce insulin resistance could be useful in preventing NIDDM:
Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known.
We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years.
The mean (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group (P<0.001 for both comparisons between the groups). The cumulative incidence of diabetes after four years was 11 percent (95 percent confidence interval, 6 to 15 percent) in the intervention group and 23 percent (95 percent confidence interval, 17 to 29 percent) in the control group. During the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the intervention group. The reduction in the incidence of diabetes was directly associated with changes in lifestyle.
Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.
Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.
This study compared the prevalence and pattern of use of complementary and alternative medicine (CAM) in individuals with and without diabetes and identified factors associated with CAM use.
The 1996 Medical Expenditure Panel Survey, a nationally representative sample of the U.S. noninstitutionalized civilian population, was analyzed. Estimates of CAM use in individuals with common chronic conditions were determined, and estimates of CAM use in patients with diabetes were compared with that in individuals with chronic medical conditions. Patterns of use and costs of CAM use in patients with diabetes were compared with those in nondiabetic individuals. Multiple logistic regression was used to determine independent predictors of CAM use in individuals with diabetes, controlling for age, sex, race/ethnicity, household income, educational level, and comorbidity.
Individuals with diabetes were 1.6 times more likely to use CAM than individuals without diabetes (8 vs. 5%, P < 0.0001). In the general population, estimates of CAM use were not significantly different across selected chronic medical conditions, but diabetes was an independent predictor of CAM use. Among individuals with diabetes, older age (> or =65 years) and higher educational attainment (high school education or higher) were independently associated with CAM use.
Diabetes is an independent predictor of CAM use in the general population and in individuals with diabetes. CAM use is more common in individuals aged > or =65 years and those with more than high school education.
To evaluate whether homeostasis model assessment-estimated insulin resistance (HOMA-IR) is an independent predictor of cardiovascular disease (CVD) in type 2 diabetes.
Conventional CVD risk factors (sex, age, smoking, plasma lipids, blood pressure, and metabolic control) and insulin resistance (estimated by HOMA) were evaluated at baseline in 1,326 patients with type 2 diabetes examined within the Verona Diabetes Complications Study. At baseline and after a mean follow-up of 4.5 years, CVD was assessed by medical history, physical examination, electrocardiography, and echo-Doppler of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow-up were carefully scrutinized to identify cardiovascular deaths. In statistical analyses, CVD was an aggregate end point including both fatal and nonfatal coronary, cerebrovascular, and peripheral vascular disease as well as ischemic electrocardiographic abnormalities and vascular lesions identified by echo-Doppler.
At baseline, 441 subjects were coded positive for CVD (prevalent cases). Incident cases numbered 126. Multiple logistic regression analyses showed that, along with sex, age, smoking, HDL/total cholesterol ratio, and hypertension, HOMA-IR was an independent predictor of both prevalent and incident CVD. A 1-unit increase in (log)HOMA-IR value was associated with an odds ratio for prevalent CVD at baseline of 1.31 (95% CI 1.10-1.56, P = 0.002) and for incident CVD during follow-up of 1.56 (95% CI 1.14-2.12, P < 0.001).
HOMA-IR is an independent predictor of CVD in type 2 diabetes. The improvement of insulin resistance might have beneficial effects not only on glucose control but also on CVD in patients with type 2 diabetes.
To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes.
We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale.
A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported.
There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.
To examine whether decreased serum levels of adiponectin are an independent risk factor for the progression to type 2 diabetes in a Japanese population.
The serum levels of adiponectin and tumor necrosis factor-alpha (TNF-alpha) at baseline (from 1995 to 1997) were evaluated in 1,792 individuals (1,023 women and 769 men, aged 58.5 +/- 12.5 years) from a cohort population (n = 3,706) of the Funagata study. Glucose tolerance was evaluated at baseline and also at 5-year follow-up examinations (n = 978, follow-up rate, 54.6%) according to the 1985 World Health Organization criteria. The correlation of clinical traits with serum levels of adiponectin was examined. The association of the traits with the progression to type 2 diabetes at the 5-year follow-up was also examined.
Among the traits examined, the correlation with aging was highest (r = 0.312, P < 0.001). Eighteen subjects with normal glucose tolerance (NGT) developed diabetes, and 709 remained NGT at the 5-year follow-up examinations. The subjects who became diabetic had decreased serum levels of adiponectin (7.29 +/- 2.35 vs. 9.13 +/- 2.35 10 x log microg/ml, P = 0.009). Multiple logistic regression analysis with age, sex, waist-to-hip ratio, and 2-h plasma glucose as the variables revealed that serum adiponectin level (odds ratio [per 0.1 log microg/ml] 0.766, P = 0.029) was an independent risk factor for the progression to type 2 diabetes. The subjects whose serum levels of adiponectin were in the lowest tertile were 9.320 times (95% CI 1.046-83.1) more likely to develop diabetes than those in the highest tertile (P = 0.046).
Decreased serum adiponectin level is an independent risk factor for progression to type 2 diabetes.
The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer.
We examined whether beta-(1-6)-D: -glucan extracted from A. blazei is a potential anticancer agent in an in vitro and in vivo animal model.
Here we show that (1) beta-glucan had cytotoxic effect against human ovarian cancer HRA cells, but not against murine Lewis lung cancer 3LL cells, in vitro; (2) beta-glucan promotes p38 MAPK activity for suppressing HRA cell proliferation and amplifying the apoptosis cascade; (3) beta-glucan stimulates translocation of the proapoptotic protein, Bax, from the cytosol to mitochondria, cytochrome c release, and subsequent caspase-9 activation; (4) treatment with SB203580, a p38 MAPK-specific inhibitor, suppresses beta-glucan-induced effects, indicating that activation of p38 MAPK is involved in the suppression of cell proliferation and mitochondrial activation-mediated cell death pathway; (5) in mice, oral supplementation with beta-glucan reduces pulmonary metastasis of 3LL cells and peritoneal disseminated metastasis of HRA cells and inhibits the growth of these metastatic tumors in lung or peritoneal cavity, in part, by suppressing uPA expression; and (6) in an in vivo experimental metastasis assay, however, the oral supplementation with beta-glucan after i.v. tumor cell inoculation did not reduce the number of lung tumor colonies.
Treatment with beta-glucan may be beneficial for cancer patients with or at risk for metastasis. The beta-glucan-dependent signaling pathways are critical for our understanding of anticancer events and development of cancer therapeutic agents.
To review evidence supporting use of thiazolidinediones (TZDs) in management of type 2 diabetes mellitus (DM2).
A MEDLINE search found several randomized controlled trials (level I evidence). No systematic reviews of these trials were found in the Cochrane Library.
Thiazolidinediones lower hemoglobin AIc levels by as much as 1.0% to 1.5%. Effects can be seen in as little as 4 weeks, but full lowering takes 6 to 12 weeks. When used in combination with other diabetic agents, such as sulfonylureas and biguanides, TZDs' hypoglycemic effects appear to be complementary. Thiazolidinediones directly improve insulin sensitivity and recovery of pancreatic beta cell function. Nevertheless, there is no evidence indicating that TZDs are superior to other antidiabetic agents currently available or that TZDs reduce the long-term complications of DM2.
Ongoing trials will further define the role of TZDs in management of diabetic patients. In current practice, cost is often a factor in the decision to prescribe TZDs.
Insulin resistance is an independent risk factor for arteriosclerosis and cardiovascular mortality. However, the mechanism by which insulin resistance contributes to arteriosclerosis is unknown. Conceivably, endothelial dysfunction could be involved. Therefore, we asked whether therapy for insulin resistance ameliorates any endothelial dysfunction.
We performed a double-blind cross-over trial of 12 patients with recently diagnosed type 2 diabetes. They received rosiglitazone 4 mg b.i.d. for 12 weeks and nateglinide 60 mg b.i.d. for the same number of weeks in random order. To assess the degree of endothelial dysfunction, we used venous occlusion plethysmography. We studied vasodilation in response to acetylcholine (ACh) with and without exogenous insulin. The agents were infused into the brachial artery. Furthermore, we determined insulin resistance by euglycemic clamp.
Glycemic control was comparable under rosiglitazone and nateglinide. Rosiglitazone ameliorated insulin resistance by 60% compared with nateglinide. ACh response was significantly increased after rosiglitazone treatment (maximum forearm blood flow 12.8 +/- 1.3 vs. 8.8 +/- 1.3 ml/100 ml after rosiglitazone and nateglinide, respectively; P < 0.05) but did not attain the level of healthy control subjects (14.0 +/- 0.7 ml/100 ml). Coinfusion of exogenous insulin increased ACh response further in the rosiglitazone group. N-monomethyl-L-arginine-acetate (L-NMMA), an antagonist of nitric oxide synthase, largely prevented the increased vasodilation after rosiglitazone, regardless of the presence or absence of insulin. Insulin sensitivity and blood flow response were found to be correlated (P < 0.01).
Insulin resistance is a major contributor toward endothelial dysfunction in type 2 diabetes. Both endothelial dysfunction and insulin resistance are amenable to treatment by rosiglitazone.
CS-045 is a new oral antidiabetic agent that was effective in insulin-resistant diabetic animal models, including the KK mouse, the ob/ob mouse, and the Zucker fatty rat. CS-045 was not effective in the streptozocin-treated mouse, an insulin-deficient diabetic animal model. In fed KK mice, CS-045 lowered the plasma glucose levels in a dose-dependent manner after a single oral administration, and the hypoglycemic effect lasted for at least 18 h. In normal rats, however, plasma glucose levels were not changed after administration of CS-045. CS-045 when given chronically (2 wk) to diabetic KK and ob/ob mice as a 0.2% food admixture dramatically improved hyperglycemia, hyperinsulinemia, and hypertriglyceridemia to near-normal values and decreased plasma lactate, free fatty acid, and ketone body levels without reducing food intake or body weight. In the obese Zucker fatty rat, oral administration of CS-045 had a similar effect in lowering plasma glucose, insulin, triglyceride, free fatty acid, lactate, and ketone body levels. The CS-045-treated Zucker fatty rats showed increased glucose tolerance and decreased insulin secretion in response to oral glucose. After 9 days of treatment, insulin binding to adipocyte plasma membranes from both CS-045-treated Zucker fatty rats and KK mice was increased. Furthermore, 2-deoxyglucose uptake in CS-045-treated adipocytes was increased and the insulin dose-response curve was shifted to the left. These findings suggest that CS-045 increases not only insulin sensitivity but also insulin responsiveness. Based on its pharmacological profile, CS-045 is a new orally effective antidiabetic agent that may reduce abnormalities of glucose and lipid metabolism in obese and non-insulin-dependent diabetes mellitus patients with insulin resistance.
The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
The thiazolidinediones are a unique class of compounds that exert direct effects on the mechanisms of insulin resistance and result in improved insulin action and reduced hyperinsulinemia. Troglitazone is the first of these compounds to be approved for use in humans and has the potential not only to reduce glycemia and insulin requirements in type II diabetes but to improve other components of the insulin resistance syndrome including dyslipidemia, hypertension, and accelerated cardiovascular disease. Such compounds also hold promise for the prevention of type II diabetes and for the treatment of other insulin-resistant states including polycystic ovary disease. In addition to the novel mechanism of action through binding and activation of PPARs, troglitazone has other unique advantages, including once-a-day administration, a low incidence of minor side effects, no known drug interactions, hepatic metabolism and secretion, and potent antioxidant properties. Thiazolidinedione compounds such as troglitazone provide an important additional resource for the health care provider in the management of type II diabetes and other components of the insulin resistance syndrome.
Currently, some natural herbal extracts are believed to have a marked tumoricidal effect and low toxicity for normal tissues. We investigated the effect of relatively low molecular weight products extracted from the basidiomycete, Agaricus blazei Murill, on MethA tumor cell growth with the aim of producing synthetic derivatives based on these products. Inoculation of the low molecule fraction (LM) into the primary tumor of a two-tumor model resulted in the marked inhibition of the tumor, not only in the right flank, but also in the non-injected left flank. Chromatographic purification and physicochemical characterization showed the main tumoricidal activity to be located in a low molecule fraction-3 (LM-3), containing alpha-1,4-glucan-beta-1,6-glucan complex with an average molecular weight of 20 kDa. A11 LM fractions and crude ATF showed in vitro selective cytotoxicity for MethA tumor cells, having no effect on normal cells. Serum levels of immunosuppressive acidic protein (IAP) in mice receiving LM fractions, particularly LM-3, significantly increased, indicating the possible activation of granulocytes. We speculate that the inhibition of the distant tumor might be due to the increased migration of granulocytes, enhanced by the effect of extract injections at the primary tumor site.
Rosiglitazone maleate is the second approved oral hypoglycemic agent of the thiazolidinedione class. The first, troglitazone, has been associated with liver failure, occasionally resulting in liver transplantation or death. There have been no reports to date of rosiglitazone-associated elevations in the alanine aminotransferase level or hepatotoxicity.
To report the clinical characteristics of liver failure developing in a patient receiving rosiglitazone.
Case report.
University hospital.
69-year-old man taking rosiglitazone, 4 mg/d.
Discontinuation of rosiglitazone therapy and treatment with lactulose, vitamin K, fresh frozen plasma, ventilatory assistance, and intensive care unit support.
Blood test monitoring, including toxicology screening, liver function tests, coagulation studies, serum chemistries, and complete blood counts.
After 21 days of rosiglitazone therapy, hepatic failure developed. Other causes of hepatic failure, such as viruses and toxins, were excluded, although it is possible that congestive heart failure was also a causative factor. The patient recovered fully with supportive care.
Rosiglitazone may be associated with hepatic failure.
Anti-viral activities of Agaricus blazei Murill were investigated. The water extracts of the cultured mycelia and fruiting bodies were fractionated with different concentrations of ethanol. To several viruses which have cytopathic effects (CPE) on VERO cells, inhibition of these effects by the ethanol fractions was tested. Strong inhibition of CPE induced by western equine encephalitis (WEE) virus was observed in the mycelial fractions but not those of fruiting bodies.
Adipose tissue performs complex metabolic and endocrine functions. This review will focus on the recent literature on the biology and actions of three adipocyte hormones involved in the control of energy homeostasis and insulin action, leptin, acylation-stimulating protein, and adiponectin, and mechanisms regulating their production. Results from studies of individuals with absolute leptin deficiency (or receptor defects), and more recently partial leptin deficiency, reveal leptin's critical role in the normal regulation of appetite and body adiposity in humans. The primary biological role of leptin appears to be adaptation to low energy intake rather than a brake on overconsumption and obesity. Leptin production is mainly regulated by insulin-induced changes of adipocyte metabolism. Consumption of fat and fructose, which do not initiate insulin secretion, results in lower circulating leptin levels, a consequence which may lead to overeating and weight gain in individuals or populations consuming diets high in energy derived from these macronutrients. Acylation-stimulating protein acts as a paracrine signal to increase the efficiency of triacylglycerol synthesis in adipocytes, an action that results in more rapid postprandial lipid clearance. Genetic knockout of acylation-stimulating protein leads to reduced body fat, obesity resistance and improved insulin sensitivity in mice. The primary regulator of acylation-stimulating protein production appears to be circulating dietary lipid packaged as chylomicrons. Adiponectin increases insulin sensitivity, perhaps by increasing tissue fat oxidation resulting in reduced circulating fatty acid levels and reduced intramyocellular or liver triglyceride content. Adiponectin and leptin together normalize insulin action in severely insulin-resistant animals that have very low levels of adiponectin and leptin due to lipoatrophy. Leptin also improves insulin resistance and reduces hyperlipidemia in lipoatrophic humans. Adiponectin production is stimulated by agonists of peroxisome proliferator-activated receptor-gamma; an action may contribute to the insulin-sensitizing effects of this class of compounds. The production of all three hormones is influenced by nutritional status. These adipocyte hormones, the pathways controlling their production, and their receptors represent promising targets for managing obesity, hyperlipidemia, and insulin resistance.
Adiponectin is a collagen-like circulating protein secreted by adipocytes that is proposed to mediate obesity-related resistance to insulin. In a case-control series, we assessed the role of adiponectin in later development of type 2 diabetes in 70 patients who later developed type 2 diabetes and 70 controls, matched for body-mass index, age, and sex. Cases and controls were taken from the longitudinal study of health in the Pima Indian population. At baseline, the concentration of adiponectin was lower in cases than in controls (p=0.01) and individuals with high concentrations of this protein were less likely to develop type 2 diabetes than those with low concentrations (incidence rate ratio 0.63 [95% CI 0.43-0.92]; p=0.02).
We investigated the immunopotentiating activities of boiled water-soluble extracts from desiccated Agaricus blazei Murill (ABM). Effect of ABM extract on antibody production was investigated by method of hemolytic plaque-forming cells (PFC) against sheep red blood cells (SRBC) antigen. ABM extracts significantly (p<0.01) increased the number of PFC in spleen with intraperitoneal administration at doses of 25 mg/kg as compared with control group. The populations of Mac-1- or CD25-positive cells significantly (p<0.01, p<0.001) increased, but in CD19-positive cells, there were no differences in ABM-treated mice as compared with control mice. The expressions of IL-6 and IL-1beta mRNA were augmented by ABM extract in both peritoneal macrophages and spleen cells. These results suggested that ABM extract might be an effective stimulator for T cell and macrophage to IL-1beta and IL-6 release, resulting in augmentation of antibody production against SRBC antigen.
To assess the independent associations of a broad range of early life risk factors and adult obesity with adult insulin resistance.
This was a cross-sectional study of 1,394 women, aged 60-79 years, from 23 British towns.
There was a strong (independent of confounding factors, other early life factors, and adult waist-to-hip ratio) inverse association between birth weight and insulin resistance in women in the highest third of BMI (>28.77 kg/m2): -0.12 (95% CI -0.19 to -0.04) log homeostasis model assessment (HOMA) score per 1 SD birth weight, but no association between birth weight and insulin resistance in women in the two lowest thirds of BMI (P for interaction = 0.04). Offspring birth weight, own leg length, and childhood manual social class did not interact with adult obesity and were all independently inversely associated with insulin resistance: -0.05 (-0.09 to -0.01) log HOMA score per 1 SD offspring birth weight, -0.09 (-0.12 to -0.06) log HOMA score per 1 SD leg length, and a -0.07 (-0.14 to 0.00) difference in log HOMA score between manual and nonmanual childhood social class. Childhood manual social class and shorter leg length were both independently associated with adverse lipid profiles. BMI and waist-to-hip ratio were independently positively associated with insulin resistance and with all other components of the insulin resistance syndrome.
Insulin resistance is an important risk factor for type 2 diabetes and coronary heart disease. Our results suggest that genetic factors, intrauterine environment, early childhood, and adult environmental factors are all relevant in determining adult insulin resistance.
Adiponectin is an adipocyte-derived peptide, which has anti-inflammatory and insulin-sensitising properties. We designed a nested case-control study to assess whether baseline adiponectin concentrations in plasma are independently associated with risk of type 2 diabetes. We found that adiponectin concentrations in plasma were lower among individuals who later developed type 2 diabetes than among controls (mean 5.34 microg/mL [SD 3.49] vs 6.87 microg/mL [4.58], p<0.0001). High concentrations of adiponectin were associated with a substantially reduced relative risk of type 2 diabetes after adjustment for age, sex, waist-to-hip ratio, body-mass index, smoking, exercise, alcohol consumption, education, and glycosylated haemoglobin A(1c) (odds ratio 4th vs 1st quartile 0.3 [95% CI 0.2-0.7], p=0.0051). We conclude that adiponectin is independently associated with a reduced risk of type 2 diabetes in apparently healthy individuals.
Agaricus blazei Murill is a medicinal mushroom native to Brazil. The present work assessed the clastogenic and anticlastogenic potential of organic extracts (ethanol and chloroform/methanol) from the lineage AB97/11 in chinese hamster CHO-K(1) (wild type) and CHO-xrs5 (repair deficient) cells using the chromosome aberration (CA) and sister chromatid exchange (SCE) assays. In these experimental conditions were observed: (a) anticlastogenic effect at concentrations of 0.06 and 0.09% of the EtOH extract and at the 0.03 and 0.06% concentrations of the C/MetOH extract in CHO-K(1); (b) absence of protector effect on CHO-xrs5 cells; and (c) absence of protector effect in the SCE assay. These results indicate that organic extracts of A. blazei lineage AB97/11 present bio-antimutagenic type protective activity.
DNA vaccines induce protective humoral and cell-mediated immune responses in several animal models. Agaricus blazei Murill (ABM) is particularly rich in polysaccharides, and has shown particularly strong results in treating and preventing cancers. The goal of this study was to investigate whether co-immunization of the fungus ABM with hepatitis B virus (HBV) core DNA vaccine could increase the immune responses. Compared with the control mice which received hepatitis B virus core antigen (HBcAg) alone, significant increase in not only the HBcAg-specific antibody response but also T cell proliferation was observed in mice which received HBcAg DNA vaccine plus ABM extract. These results suggest that ABM extract might represent an adjuvant to improve the efficacy of DNA vaccines in vivo.
Agaricus blazei Murill, popularly known as "Sun Mushroom" or "Himematsutake", is native to Brazil. Nowadays, this mushroom has been target of great scientific interest due to its medical power and because it has shown antitumoral and immune modulatory properties. This work evaluated the mutagenic and antimutagenic potential from aqueous extracts prepared in different temperatures (4 degrees C, 25 degrees C and 60 degrees C) from the lineage AB 97/29 in two basidiocarp phases (young and sporulated) and from A. blazei commercialized in Londrina-PR-Brazil, named here as AB PR, and in Piedade-SP-Brazil, named as AB SP. Both micronucleus (MN) as comet assays were used. Chinese hamster lung V79 cells were treated in three antimutagenic experimental protocols: pre-, post- and simultaneous treatments, with the aqueous extracts of the A. blazei Murill and methyl methanesulfonate (MMS). The results suggested that under these circumstances of treatment, aqueous extracts of the A. blazei in both assays did not show any genotoxic potential. However, by the MN test, an antigenotoxic effect was shown against mutagenicity inducted by MMS for aqueous extracts at 60 degrees C of mushroom commercialized in Piedade- SP, in pre-, post- and simultaneous treatments and for AB PR only when used in pre-treatment. On the other hand, with comet assay, the results showed no protective effect in any case. The numbers indicated that different results can be get from A. blazei teas, and that not all of them seemed to be an efficient antimutagen against the induction of micronuclei by MMS.
Adiponectin, synthesized in the adipose tissue, appears to play an important role in hyperglycemia and dyslipidemia, as well as in inflammatory mechanisms, which lead to a markedly increased atherosclerotic risk in diabetic subjects. However, previous studies did not evaluate the complex relationships between adiponectin and the array of metabolic abnormalities commonly observed in diabetes.
To examine the associations between plasma levels of adiponectin and HbA(1c), blood lipids, and inflammatory markers, we obtained blood samples from 741 participants in the Health Professionals Follow-up Study with a diagnosis of type 2 diabetes.
Plasma adiponectin levels were positively correlated with HDL cholesterol and negatively correlated with triglycerides, apolipoprotein B-100 (apoB(100)), C-reactive protein (CRP), and fibrinogen. These associations were not appreciably altered after controlling for lifestyle exposures, medical conditions, and obesity-associated variables. A 10-microg/ml higher level of plasma adiponectin was associated with lower HbA(1c) (-0.21% points, P = 0.001), triglycerides (-0.39 mmol/l, P < 0.001), apoB(100) (-0.04 g/l, P < 0.001), CRP (-0.51 mg/l, P = 0.003), and fibrinogen (-0.53 micromol/l, P < 0.001) and higher HDL cholesterol (0.13 mmol/l, P < 0.001). Associations between adiponectin and inflammatory markers were furthermore independent of HbA(1c) and HDL cholesterol, suggesting that the anti-inflammatory properties of adiponectin are not mediated by potential effects on glycemic control and blood lipids. Our results were consistent among obese and nonobese men.
Our study supports the hypothesis that increased adiponectin levels might be associated with better glycemic control, better lipid profile, and reduced inflammation in diabetic subjects. Measures that increase adiponectin levels might be valuable targets for decreasing the atherosclerotic risk present in diabetes.
A mushroom extract, Agaricus blazei Murill Kyowa (ABMK), has been reported to possess antimutagenic and antitumor effects. Here, we investigate the beneficial effects of ABMK consumption on immunological status and qualities of life in cancer patients undergoing chemotherapy. One hundred cervical, ovarian, and endometrial cancer patients were treated either with carboplatin (300 mg / m(2)) plus VP16 (etoposide, 100 mg / m(2)) or with carboplatin (300 mg / m(2)) plus taxol (175 mg / m(2)) every 3 weeks for at least three cycles with or without oral consumption of ABMK. We observed that natural killer cell activity was significantly higher in ABMK-treated group (ANOVA, n = 39, P < 0.002) as compared with nontreated placebo group (n = 61). However, no significant difference in lymphokine-activated killer and monocyte activities was observed in a manner similar to the count of specific immune cell populations between ABMK-treated and nontreated groups. However, chemotherapy-associated side effects such as appetite, alopecia, emotional stability, and general weakness were all improved by ABMK treatment. Taken together, this suggests that ABMK treatment might be beneficial for gynecological cancer patients undergoing chemotherapy.
We previously found that ergosterol isolated from Agaricus blazei inhibited tumor growth through the inhibition of tumor-induced neovascularization. In the present study, we isolated further anti-angiogenic substances (A-1 and A-2) from this fungus using an assay system of angiogenesis induced by Matrigel supplemented with vascular endothelial growth factor, and A-1 was identified as sodium pyroglutamate. Next, we examined the antitumor and antimetastatic actions of A-1 using Lewis lung carcinoma (LLC)-bearing mice. A-1 (30, 100 and 300 mg/kg) inhibited tumor growth and metastasis to the lung. The reduction of the numbers of splenic lymphocytes, CD4+ and CD8+ T cells in LLC-bearing mice was inhibited by the oral administration of A-1 (30, 100 and 300 mg/kg). Further, A-1 increased the number of apoptotic cells of tumors and the numbers of CD8+ T and natural killer cells invading the tumors, and inhibited the increase of von Willebrand factor expression (a measure of angiogenesis) in the tumors. These results suggest that the antitumor and antimetastatic actions of A-1 (sodium pyroglutamate) may be associated with inhibition of the reduction of immune response caused by the tumor growth and tumor-induced neovascularization. This is the first report showing that sodium pyroglutamate isolated from A. blazei as an anti-angiogenic substance has potent antitumor and antimetastatic actions, as well as immune-modulatory activity, in tumor-bearing mice.
Beta-glucans were prepared from Agaricus blazei Murill by repeated extraction with hot water. The average molecular weights of beta-glucans were 30-50 kDa by gel filtration chromatography. Oligosaccharides (AO), derived from hydrolyzing beta-glucans with an endo-beta-(1-->6)-glucanase from Bacillus megaterium, were mainly di- and tri-saccharides. Though beta-glucans and AO both showed anti-hyperglycemic, anti-hypertriglyceridemic, anti-hypercholesterolemic, and anti-arteriosclerotic activity indicating overall anti-diabetic activity in diabetic rats, AO had about twice the activity of beta-glucans with respect to anti-diabetic activity.
Insulin resistance underlies the pathogenesis of hyperglycaemia and cardiovascular disease in most people with type 2 diabetes. Metformin and thiazolidinediones (pioglitazone and rosiglitazone) counter insulin resistance by different cellular mechanisms and with complementary effects, making them suited for use in combination. Metformin exerts a stronger suppression of hepatic glucose output, while thiazolidinediones produce a greater increase in peripheral glucose uptake, enabling metformin-thiazolidinedione combinations to improve glycaemic control in type 2 diabetes with additive efficacy. Basal insulin concentrations are not raised by metformin or thiazolidinediones, so there is minimal risk of hypoglycaemia, and metformin can reduce the weight gain associated with thiazolidinediones. There are overlapping effects of metformin and thiazolidinediones against a range of athero-thrombotic factors and markers. These include decreased plasminogen activator inhibitor-1, reduced platelet aggregation, reductions of several vascular adhesion molecules, and reduced markers of low-grade inflammation such as C-reactive protein. Additionally, thiazolidinediones increase adiponectin and slightly reduce blood pressure. Both metformin and thiazolidinediones can improve components of the lipid profile: thiazolidinediones consistently reduce free fatty acid concentrations and decrease the proportion of small dense low-density-lipoprotein, and pioglitazone also decreases triglycerides. During co-administration, metformin and thiazolidinediones do not interfere with each other's pharmacokinetics, and lower doses of the two agents together can achieve efficacy with fewer side effects. Metformin-thiazolidinedione combinations require attention to the precautions for both agents, especially renal, cardiac and hepatic status. Thus, metformin and thiazolidinediones can be used in combination to address the hyperglycaemia and vascular risk in type 2 diabetes.
The aim was to investigate the antibacterial effect of the biologically active and edible mushroom Agaricus blazei Murill (AbM). A water extract of AbM or PBS control was administered orally before or with challenge to NIH/OlaHsd mice, experimentally infected intraperitoneally with the moderately virulent Streptococcus pneumoniae serotype 6B. End points were bacteraemia and survival rate. The AbM extract, protected against systemic S. pneumoniae 6B infection in the mice. It was most effective when given 24 h before inoculation but did also have protective effects when given together with challenge compared with control. The lack of antibiotic effect on pneumococci in vitro and increased levels of cytokines MIP-2 and TNF-alpha in the serum of mice receiving AbM extract, indicated that the protective effect of AbM was due to the involvement of the native immune system. This is the first report of anti-infection effects of AbM in vivo. Our results suggest that AbM extract may be useful as additional prophylactic and possibly therapeutic treatment against bacterial and possibly other infections in humans.
To assess the association between complementary and alternative medicine (CAM) use, preventive care practices, and use of conventional medical services among adults with diabetes.
We analyzed data on 2,474 adults with diabetes. We created an overall CAM-use category based on use of any of the following: diets, herbs, chiropractic care, yoga, relaxation, acupuncture, ayuverda, biofeedback, chelation, energy healing, Reiki therapy, hypnosis, massage, naturopathy, and homeopathy. We used multiple logistic regression to assess the effect of CAM use on preventive care practices (receipt of influenza and pneumonia vaccines) and use of conventional medical services (number of primary care and emergency department visits). STATA was used for statistical analysis to account for the complex survey design.
A total of 48% of adults with diabetes used some form of CAM. CAM use was independently associated with receipt of pneumonia vaccination (odds ratio 1.56 [95% CI 1.26-1.94]) but not significantly associated with receipt of influenza vaccination (1.17 [0.92-1.48]). CAM use was independently associated with visiting the emergency department (1.34 [1.06-1.70]), having six or more primary care visits (1.44 [1.14-1.83]), and having eight or more primary care visits (1.66 [1.22-2.25]).
In contrast to the findings of previous studies, CAM use appears to be associated with increased likelihood of receipt of preventive care services and increased emergency department and primary care visits. CAM use may not be a barrier to use of conventional medical services in adults with diabetes.
The Agaricus blazei Murill (ABM) mushroom, known as the sun mushroom, is native to Brazil and has become known for its medicinal properties. This study examined the anticlastogenic effect of Agaricus blazei in Chinese hamster ovary cells, CHO-k1, by means of a chromosome aberration test using methyl methanesulphonate (MMS, 10(-4)M) as the DNA damage inducing agent. Two mushroom lines were used, ABM 99/26 and ABM 97/11, and the latter was used in the young (Y) and sporulating (S) developmental phases. The cells were treated for 12 h with MMS alone or combined with aqueous extracts of A. blazei at a final concentration of 0.15%, which were prepared at three different temperatures: (a) hot (60 degrees C), (b) room temperature (25 degrees C) and (c) chilled (4 degrees C). Mushroom extracts showed a marked anticlastogenic effect against DNA damage, as evidenced by a decrease in the number of cells with breaks, regardless of the line used, or the developmental stage or the temperature at which the extract was prepared. Generally, the extracts were more effective in reducing the isochromatid type breaks. The data obtained suggest that extracts of A. blazei mushroom are anticlastogenic under the conditions tested, mainly during the G1 and S stages of the cell cycle, where chromosome breaks of the isochromatid type are produced by the MMS agent.
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