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Hypoglycemic effects of Ganoderma lucidum polysaccharides in type 2 diabetic mice
Abstract
Our aims were to investigate the hypoglycemic effects and mechanisms of action of Ganoderma lucidum polysaccharides (GLPs) administered for 7 days in type 2 diabetic mice. The mice were randomly divided into four groups (8 mice/group): normal control group, diabetic control group, low-dose GLP-treated diabetic group (50 mg/kg/d), and high-dose GLP-treated diabetic group (100 mg/kg/d). Diabetes was induced by streptozotocin injection and high-fat dietary feeding. At the end of the study, fasting serum glucose, insulin, body weight (BW) and epididymal white adipose tissue weight were measured. The hepatic mRNA levels of glycogen phosphorylase (GP), fructose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes were determined by real-time polymerase chain reaction. Both doses of GLPs significantly decreased fasting serum glucose, insulin and epididymal fat/BW ratio compared with the diabetic control group (p < 0.05). The hepatic mRNA levels of GP, FBPase, PEPCK and G6Pase were significantly lower in both GLP-treated groups compared with the diabetic control group. Taken together, GLPs significantly decrease fasting serum glucose levels in type 2 diabetic mice in a dose-dependent manner. The decreases in fasting serum glucose levels may be associated with decreased mRNA expression levels of several key enzymes involved in gluconeogenesis and/or glycogenolysis.
... Although several studies have reported the hypoglycaemic and antioxidant potentials of G. lucidum fruiting bodies (He et al. 2006;Seto et al. 2009;Xiao et al. 2012;Zheng et al. 2012;Pan et al. 2013;Bach et al. 2018), the composition and relative proportions of G. lucidum basidiocarp cultivation are different from those of submerged culture (Wachtel-Galor et al. 2011). In addition, the yield of mycelia and extracellular polysaccharides obtained from submerged G. lucidum cultures varies with the culture conditions (Chang et al. 2006). ...
... In addition, many identified bioactive constituents in G. lucidum fruiting bodies, such as polysaccharides, proteoglycans, proteins, ganoderic acids, and triterpenoids, have been shown to exhibit hypoglycaemic activities (Ma et al. 2015). Polysacc harides inhibited hyperglycaemia by regulating the expression of several key enzymes in the glucose metabolism pathway, such as hepatic glucokinase, phosphofructokinase, G6PD, hepatic glycogen phosphorylase, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and G6Pase (Xiao et al. 2012). G. lucidum proteoglycan could inhibit the activity of protein tyrosine phosphatase (PTP) 1B, a promising therapeutic target in diabetes, and ameliorated plasma glucose in db/db mice ). ...
... Polysaccharides are among the major extracellular components contained in whole submerged G. lucidum cultures, and polysaccharide intake was calculated as 36 and 107 mg/kg/day for rats in the 1 G and 3 G groups, respectively. Xiao et al. (2012) have reported that daily treatment with polysaccharides extracted from G. lucidum fruiting bodies (50-100 mg/kg) significantly decreases fasting serum glucose levels in rats with type 2 diabetes in a dosedependent manner. Most importantly, the hypoglyc aemic effect of polysaccharides has been associated with decreased expression of several key enzymes involved in gluconeogenesis and/or glycogenolysis (Xiao et al. 2012). ...
We aim to investigate the hypoglycaemic and antioxidant effects of submerged Ganoderma lucidum cultures and elucidate the potential mechanisms behind these effects using a type 2 diabetic rat model. Diabetic rats were daily fed with a high-fat diet supplemented with 1% or 3% freeze-dried whole submerged cultures of G. lucidum or mycelia for 5 weeks. We observed significantly decreased fasting plasma glucose levels, homoeostasis model assessment equation-insulin resistance, and plasma glucose in oral glucose tolerance test. Furthermore, we observed increased levels of glycogen, hepatic hexokinase, glucose-6-phosphate dehydrogenase, and intestinal disaccharidase activities. G. lucidum supplement downregulated the plasma levels of aspartate aminotransferase, alanine aminotransferase, creatinine, and urea nitrogen as well as liver and kidney levels of thiobarbituric acid reactive substances. Based on the hypoglycaemic and antioxidant effects of G. lucidum submerged cultures, we recommend the potential application of these products as functional foods or additives for controlling type 2 diabetes.
Abbreviations ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BUN: Blood urea nitrogen; BW: Body weight; CREA: Creatinine; FPG: Fasting plasma glucose; G6Pase: Glucose-6-phosphatase; G6PD: Glucose-6-phosphate dehydrogenase; HOMA-IR: Homoeostasis model assessment of insulin resistance; OGTT: Oral glucose tolerance test; PTP: Protein tyrosine phosphatase; STZ: Streptozotocin; TBARS: Thiobarbituric acid reactive substances
... These two carboxylate bands were not strongly pronounced in the FTIR spectrum of F2b; therefore, this sub-fraction contained fewer uronic acids. The spectra of both sub-fractions have several bands at 1375, 1315, 1155, 1075, 1040, and 895 cm −1 characteristic for β-anomeric glucose units and, therefore, β-glucans [65][66][67][68][69]. and pronase was used. ...
... These two carboxylate bands were not strongly pronounced in the FTIR spectrum of F2b; therefore, this sub-fraction contained fewer uronic acids. The spectra of both sub-fractions have several bands at 1375, 1315, 1155, 1075, 1040, and 895 cm −1 characteristic for β-anomeric glucose units and, therefore, β-glucans [65][66][67][68][69]. ...
In this study, we focused on the isolation and structural characterization of polysaccharides from a basidiocarp of polypore fungus Ganoderma resinaceum. Polysaccharide fractions were obtained by successive extractions with cold water at room temperature (20 °C), hot water under reflux (100 °C), and a solution of 1 mol L−1 sodium hydroxide. The purity of all fractions was controlled mainly by Fourier transform infrared (FTIR) spectroscopy, and their composition and structure were characterized by organic elemental analysis; neutral sugar and methylation analyses by gas chromatography equipped with flame ionization detector (GC/FID) and mass spectrometry detector (GC/MS), respectively; and by correlation nuclear magnetic resonance (NMR) spectroscopy. The aqueous extracts contained two main polysaccharides identified as a branched O-2-β-d-mannosyl-(1→6)-α-d-galactan and a highly branched (1→3)(1→4)(1→6)-β-d-glucan. Mannogalactan predominated in the cold water extract, and β-d-glucan was the main product of the hot water extract. The hot water soluble fraction was further separated by preparative anion exchange chromatography into three sub-fractions; two of them were identified as branched β-d-glucans with a structure similar to the corresponding polysaccharide of the original fraction. The alkaline extract contained a linear (1→3)-α-d-glucan and a weakly branched (1→3)-β-d-glucan having terminal β-d-glucosyl residues attached to O-6 of the backbone. The insoluble part after all extractions was identified as a polysaccharide complex containing chitin and β-d-glucans.
... - Ma et al., 2015, Ratnaningtyas et al., 2018, Xiao et al., 2012. -Increase antioxidant enzymes such as glutathione peroxidase and superoxide dismutase. ...
... The first three forms are the main active compounds that serve as the anti-hyperglycemic compounds due to the ability to synthesize glutathione that serves as an antioxidant against dialuric acid and ROS production that damage β-cell of the pancreas with increased glycolysis and ATP production (Ratnaningtyas et al., 2018). Administration of 50 mg/kg Ganoderma lucidum powder in diabetic rates resulted in the reduction of serum glucose level by 39%, whereas consumption of 100 mg/kg resulted in a 52% reduction (Xiao et al., 2012). Recently, the similar result was reported by Ratnaningtyas et al. (2018) who concluded that consumption of Ganoderma lucidum in high concentration (1000 mg/kg) effectively reduced serum glucose level by 63.49% while, the lower concentration (250 mg/kg) reduced serum glucose level by 44.27. ...
... A further polysaccharide, composed of glucose, mannose, xylose, arabinose, galactose, and ribose in the following ratio: 68.45:15.87:4.71:4.08:3.78:3.11, was isolated from G. lucidum in 2012 [69,74]. For 7 days, Xiao studied the effects of G. lucidum polysaccharides at 50 and 100 mg/kg/day in mice with streptozotocin-induced diabetes. ...
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.
... It is a glucose tolerance test, which is used to determine the function of islet β-cells and the ability of the body to regulate blood glucose level. Diabetic patients need to secrete more insulin in the environment of long-term hyperglycemia, which will reduce ISI and cause IR. 21 In summary, we hypothesized that walnut-derived peptides may be involved in the process of glucose metabolism, thereby reducing blood glucose level, inhibiting weight loss, regulating insulin sensitivity, and ameliorating IR. Consistent with this, Dou et al. reported that whey protein peptides alleviated weight loss, reversed dyslipidemia, and suppressed inflammatory responses in T2DM mice. ...
Autophagy flux plays a significant protective role in type 2 diabetes mellitus (T2DM). However, the mechanisms by which autophagy mediates insulin resistance (IR) to ameliorate T2DM remain unclear. This study explored the hypoglycemic effects and mechanisms of walnut-derived peptides (fraction 3-10 kDa and LP5) in streptozotocin and high-fat-diet-induced T2DM mice. Findings revealed that walnut-derived peptides reduced the levels of blood glucose and FINS and ameliorated IR and dyslipidemia. They also increased SOD and GSH-PX activities and inhibited the secretion of TNF-α, IL-6, and IL-1β. Additionally, they increased the levels of ATP, COX, SDH, and MMP of liver mitochondria. Western blotting indicated that walnut-derived peptides up-regulated LC3-II/LC3-I and Beclin-1 expression, while they down-regulated p62 expression, which may be associated with the activation of the AMPK/mTOR/ULK1 pathway. Finally, the AMPK activator (AICAR) and inhibitor (Compound C) were used to verify that LP5 could activate autophagy through the AMPK/mTOR/ULK1 pathway in IR HepG2 cells.
... GLPs decreased hepatic glucose production by down-regulation of the expression levels of gluconeonegic genes PEPCK, FBPase, and G6Pase, and increased hepatic glycogen content by down-regulation of the expression of glycogen-degrading gene GP in the liver. These results suggest that GLPs ameliorate hyperglycemia by regulation of genes expression related to glucose metabolism in liver (Xiao et al. 2012). ...
Pre-diabetes is a stage that usually precedes the onset of type 2 diabetes with a slight
increase in fasting glucose, between 5.6 and 6.9 mmol/L; decreased glucose tolerance,
between 7.8 and 11 mmol/L; and glycated hemoglobin, between 5.5 and 6.4%
(ADA 2020). These biochemical abnormalities are usually caused by defects in
insulin secretion from pancreatic cells, low insulin activity, or both (Unwin et al.
2002). Pre-diabetes can eventually lead to type 2 diabetes, which is characterized by
hyperglycemia due to the inability of cells to respond fully to insulin, or to be
resistant to insulin. Insulin resistance is characterized by insulin inefficiency in
promoting glucose uptake by tissues and low intracellular glucose concentration
signals for increased insulin production by the pancreas. Over time, depleted pancreatic
beta cells reduce or stop insulin production, further elevating blood glucose
levels (>6.9 mmol/L), characteristic of the diabetes condition. According to epidemiological
data, type 2 diabetes is common in the elderly, but its frequency has
increased in children and young adults due to high rates of obesity, sedentary
lifestyle, and unbalanced diet, with excess fat and sugar. All of these factors indicate
that both type 1 and type 2 diabetes result from a combination of genetic predisposition
and environmental triggers (IDF 2020).
Type 2 diabetes symptoms are similar to those of type 1 diabetes, but they are
difficult to be identified in the early stages due to the long pre-diagnosis process, and,
therefore, up to one third of the population may not be diagnosed early (Bansal 2015;
Kaur 2014; Buchanan et al. 2002). This can be detrimental for a favorable prognosis
after a long period of latent disease, and complications such as retinopathy or ulcers
in the lower limbs that do not heal may occur (Chiasson et al. 2002). Furthermore,visceral obesity common in overweight and obese patients is related to the local and
systemic inflammatory process, closely linked to the development of these
comorbidities (ADA 2020). Regarding the healthy population, individuals with
pre-diabetes and diabetes have a higher risk over the time of developing cardiovascular
disease, metabolic syndrome, and polycystic ovaries, in addition to higher
morbidity and mortality rates (Bansal 2015; Kaur 2014).
Considering the close relationship between pre-diabetes, obesity, and diet, it is
important to examine the influence of intestinal microbiota in this context. Intestinal
microbiota is characterized by a diverse community of bacteria responsible for
influencing nutrient metabolism, immune responses, and resistance to infectious
pathogens (Nicholson et al. 2012; Belkaid and Hand 2014; van Nood et al. 2013).
In the diabetic population, the intestinal microbiota presents a pattern of dysbiosis,
which can be the starting point for the evolution of pre-diabetes to type 2 diabetes
and other chronic diseases (Pratley 2013; Ziemer et al. 2008; Tsui et al. 2008;
Stefanakia et al. 2018). Current scientific evidence has shown that probiotics or
prebiotics, including phenolic compounds, can play a widely recognized role in the
regulation of the intestinal microbiota, altering microbial composition and the
metabolism of the bacteria and host (Tsai et al. 2019; Wang et al. 2020). Based on
these fundamentals, this chapter will address the intrinsic relationships between the
consumption of probiotics and prebiotics in individuals with pre-diabetes and type
2 diabetes.
... GLPs decreased hepatic glucose production by down-regulation of the expression levels of gluconeonegic genes PEPCK, FBPase, and G6Pase, and increased hepatic glycogen content by down-regulation of the expression of glycogen-degrading gene GP in the liver. These results suggest that GLPs ameliorate hyperglycemia by regulation of genes expression related to glucose metabolism in liver (Xiao et al. 2012). ...
The increased worldwide prevalence of pre-diabetes and diabetes, especially type 2 diabetes, requiring different strategies for their prevention and management. A new focus is the reversal of diabetes dysbiosis, a disruption of gut microbiota homeostasis, which is closely related to elevated blood glucose levels and altered metabolic parameters. In this sense, a balanced diet plays a key role, and, particularly, probiotic and prebiotic have shown a promising role. This chapter explored current knowledge on the potential of probiotic and prebiotic to modulate glucose homeostasis. We showed that the consumption of probiotics and prebiotics is a promising strategy with a beneficial impact on gut microbiota and glycemic control. Furthermore, specific probiotic strains, such as L. acidophilus, L. casei strain Shirota, and B. lactis Bb12, have demonstrated the ability to improve parameters related to pre-diabetes and type 2 diabetes. In addition, polyphenols are emerging as a new alternative in glycemic control through the production of short chain fat acids (SCFA) and decreased lipopolysaccharides (LPS) translocation that leads to metabolic endotoxemia. Finally, the ingestion of beneficial bacteria, and foods rich in fiber and polyphenols, or a combination of them, is a good strategy for the control of pre-diabetes and type 2 diabetes, but more studies are still needed, mainly clinical trials, for these strategies are improved and widely used.
... Mean serum HDL-c was also slightly improved by G. lucidum supplementation (P > 0.05); however, the changes in total cholesterol level between the two groups were significant. Surveys on previous works about these metabolic indices were inconsistent with our results; as most animal studies revealed hypoglycemic action of G. lucidum or its extracts and related components [18][19][20][21], and supplementation of G. lucidum polysaccharide had anti-diabetic effect of on type 2 diabetic patients [22]. While, evidence from other clinical trial does not support the use of G. lucidum for treatment of cardiovascular risk factors in people with diabetes mellitus or metabolic syndrome [10,12]. ...
BACKGROUND: There are growing interests in the use of medicinal mushrooms in controlling overweight and obesity. OBJECTIVE: The aim of the present study was to assess the effect of Lingzhi on anthropometric indices, fasting blood sugar, lipid profile and blood pressure of overweight individuals METHODS: This randomized double-blind clinical trial was performed on seventy-two overweight individuals (Body Mass Index (BMI) = 25–29.9 kg/m2) received 3 capsule Ganoderma Lucidum (each capsule containing 220 mg of whole powder and 30 mg of pure aqueous extract) daily or matching placebo for 6 weeks. Anthropometric indices, metabolic tests (fasting blood sugar (FBS) and serum lipid profile) and blood pressure were measured before and after treatment. RESULTS: Data analyses indicated that body weight and BMI were decreased after 6-week intervention (P < 0.05). The beneficial effect of supplementation was evident on some anthropometric indices. Changes in LDL-cholesterol were significantly different between two treatment and placebo groups (P < 0.05). FBS, other components of lipid profile and blood pressure did not significantly change by Lingzi treatment. CONCLUSIONS: Results showed that Ganoderma Lucidum might have some potential benefits on anthropometric indices and mild effects on lipid profile, but and there is no claim for weight lose function. Hence, further long-term studies are recommended.
... Furthermore, administration of Gl-PS produced hypoglycaemic effects and an improvement in lipid profile in streptozotocin-induced diabetic mice (He et al. 2006;Li et al. 2011;Zheng et al. 2012). It has been suggested that the hypoglycaemic effect is mainly through preventing apoptosis of pancreatic b-cells and enhancing b-cells regeneration (Zheng et al. 2012), and a modulation of serum insulin and hepatic mRNA levels of several key enzymes involved in gluconeogenesis and/or glycogenolysis, including GP, fructose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK), and G6Pase (Xiao et al. 2012). Xiao et al. (2017) isolated F31, a b-heteropolysaccharide with a weight-average molecular weight of 15.9 kDa, from Gl-PS. ...
Context
Various herbal medicines are thought to be useful in the management of cardiometabolic disease and its risk factors. Ganoderma lucidum (Curtis) P. Karst. (Ganodermataceae), also known as Lingzhi, has received considerable attention for various indications, including some related to the prevention and treatment of cardiovascular and metabolic disease by ameliorating major cardiovascular risk factors.
Objective
This review focuses on the major studies of the whole plant, plant extract, and specific active compounds isolated from G. lucidum in relation to the main risk factors for cardiometabolic disease.
Methods
References from major databases including PubMed, Web of Science, and Google Scholar were compiled. The search terms used were Ganoderma lucidum, Lingzhi, Reishi, cardiovascular, hypoglycaemic, diabetes, dyslipidaemia, antihypertensive, and anti-inflammatory.
Results
A number of in vitro studies and in vivo animal models have found that G. lucidum possesses antioxidative, antihypertensive, hypoglycaemic, lipid-lowering, and anti-inflammatory properties, but the health benefits in clinical trials are inconsistent. Among these potential health benefits, the most compelling evidence thus far is its hypoglycaemic effects in patients with type 2 diabetes or hyperglycaemia.
Conclusions
The inconsistent evidence about the potential health benefits of G. lucidum is possibly because of the use of different Ganoderma formulations and different study populations. Further large controlled clinical studies are therefore needed to clarify the potential benefits of G. lucidum preparations standardised by known active components in the prevention and treatment of cardiometabolic disease.
... It was found that the administration of water extracts to laboratory animals with induced diabetes significantly reduced blood glucose levels [43,75,76]. The hypoglycemic effect of polysaccharides have been extensively studied in vitro and in vivo [77][78][79]. Hypoglycemic effect of polysaccharides from G. lucidum was found in rats with streptozotocin induced diabetes [43,44]. GLP also had the ability to relieve morphotic changes in the kidneys and reduce oxidative stress. ...
Medicinal mushrooms are rich sources of pharmacologically active compounds. One of the mushrooms commonly used in traditional Chinese medicine is Ganoderma lucidum (Leyss. Ex Fr.) Karst. In Asian countries it is treated as a nutraceutical, whose regular consumption provides vitality and improves health. Ganoderma lucidum is an important source of biologically active compounds. The pharmacologically active fraction of polysaccharides has antioxidant, immunomodulatory, antineurodegenerative and antidiabetic activities. In this review, we summarize the activity of Ganoderma lucidum polysaccharides (GLP).
... Additionally, it has been reported that GLPs significantly decrease fasting serum glucose levels in T2DM mice in a dose-dependent manner (36). The decrease in fasting serum glucose levels may be associated with decreased mRNA expression level of several key enzymes, such as hexokinase, involved in gluconeogenesis and/or glycogenolysis (41). Furthermore, Xiao et al (42) demonstrated that the anti-diabetic effect of GLPs may be associated with the downregulation of hepatic glucose-regulated enzyme mRNA levels via AMPK activation. ...
Diabetes is a threat to patient health worldwide. Type 2 diabetes (T2DM), one of the two main types of diabetes, is a long-term metabolic disease caused by heredity and environmental factors. It has been reported that Ganoderma lucidum polysaccharide (GLP) significantly decreased the concentration of blood glucose, promoted insulin secretion, improved glucose tolerance and regulated the concentration of blood lipids. In the present study, a T2DM model was established in db/db mice, following which T2DM mice were treated with GLP (100 and 400 mg/kg) for 8 weeks, with MET used as the positive control. The glycosylated hemoglobin (HbAlc) and fasting blood glucose (FBG) levels, and diabetes-associated clinical chemistry indexes were detected in the blood and serum of each mouse. Hematoxylin and eosin, and oil red O staining were performed on the livers of each mouse to evaluate the level of liver fat. The expression levels of family with sequence similarity 3 (FAM3C), heat shock factor 1 (HSF1), calmodulin (CaM), AKT and phosphorylated (p)-AKT were detected in the hepatocytes of T2DM mice using reverse transcription-quantitative PCR and western blotting. The results demonstrated that the unbalanced levels of HbAlc, FBG and diabetes-related index in T2DM mice were significantly improved by treatment with GLP. Lipid droplets in the hepatocytes of mice shrank in the GLP groups compared with the model control group. The expression levels of FAM3C, HSF1, CaM and p-AKT/AKT in the hepatocytes of T2DM mice were significantly increased following treatment with GLP. In conclusion, GLP exerted significant effects on lipid metabolism in diabetes, which may be associated with the activation of the FAM3C-HSF1-CaM signaling pathway.
... The alcohol and aqueous extract of G. lucidum fruiting bodies have shown the reduced blood sugar level in diabetic mice. 35,36 Hypoglycemic effect of polysaccharides isolated from G. lucidum was observed by Xiao et al., 37 and Zhang& Lin. 38 The reduction in plasma glucose levels in steroid induced rats was concluded in the study conducted by Sarker 36 which confirms the anti-hyperglycemic, insulin-sensitivity and hyperlipidaemic activity of G. lucidum. ...
Medicinal mushrooms have been used since olden days for the treatment of various diseases.
Ganoderma lucidum or Reishi is a medicinal mushroom of significant importance which
is gaining popularity due to the presence of numerous bio-active ingredients in it. Wild
collection of this mushroom along with its cultivation is done worldwide to meet its everincreasing demand in the market. Although, artificial or sawdust method of its cultivation
on different woody substrates is commonly used but wood log cultivation method is also
in practice. The steps for its cultivation include spawn preparation, substrate preparation,
fruiting body management, harvesting and storage with their own set of requirements and
precautions for each step. Several healthcare, personal care, food and beverage products
made of its extract are being marketed and consumed worldwide. In this review, a general
understanding about the cultivation of medicinal mushroom Ganoderma lucidum, current
market scenario and its potential in Indian markets are discussed.
... immune-modulatory [6,8,9], antioxidant [10][11][12], and hypoglycemi [13] effects. Ganoderma-based drugs have been developed using these pharmaceutical properties. ...
Background:
Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damage but also strengthen the muscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin (mSC) on satellite cells (SCs), which are known as the muscle stem cells.
Methods:
The myogenic cells, included SCs (Pax7+) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridine assessed simultaneously. The molecular signal pathway was further investigated by using Western blotting and signal pathway inhibitors.
Results:
Our data revealed that 200 µg/mL mSC had an optimal capability to significantly enhance the SC proliferation. Furthermore, this enhancement of SC proliferation was verified to be involved with activation of TAK1-JNK-AP-1 signaling pathway through TLR2, whose expression on SC surface was confirmed for the first time here.
Conclusion:
Micronized sacchachitin extracted from GT was capable of promoting the proliferation of SC under a correct concentration.
... Of these, the polysaccharides (PSs) were identi ed as the major source for biological activity and therapeutic use [2][3][4]. PSs possess antitumor [5][6][7], immune-modulatory [6,8,9], antioxidant [10][11][12], and hypoglycemi [13] effects. Ganoderma-based drugs have been developed using these pharmaceutical properties. ...
Background: Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damagebut also strengthen themuscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin(mSC) on satellite cells (SCs), which are known as the muscle stem cells.
Methods: The myogenic cells, included SCs (Pax7 + ) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridineassessed simultaneously. The molecular signal pathway was further investigated by using Western blotting and signal pathway inhibitors.
Results: Our results revealed that 200 µg/mL mSC had an optimal capability to significantly enhance the SC proliferation. Furthermore, this enhancement of SC proliferation was verified to be involved with activation of TAK1-JNK-AP-1 signaling pathway through TLR2, whose expression on SC surface was confirmed for the first time here.
Conclusion: Micronized sacchachitinextracted fromGT was capable of promoting the proliferation of SC under a correct concentration.
... Moreover, the antidiabetic activity of okra could be attributed to its' bioactive components, which might contribute to inhibiting pancreatic islet cell apoptosis (Y. Zhang et al., 2014), et al., 2015), or even through pathways independent from insulin such as decreasing glucose uptake (Tang et al., 2015), and downregulating glycogen phosphorylase mRNA expression (Xiao et al., 2012). ...
The aim of the present study was to investigate the effect of okra consumption on serum levels of lipid profiles and glycemic indices in Type 2 diabetic (T2D) patients. The present study was a randomized, double‐blinded clinical trial, carried out in Kerman, Iran. Sixty T2D patients were randomized into intervention and control groups and received 10 g okra powder blended in 150 g conventional yogurt or conventional yogurt alone, along with dinner and lunch, for 8 weeks. Glycemic markers and lipid profile were assessed, as well as anthropometric measures, at the beginning and end of study. The findings showed that 8 weeks okra consumption resulted in a significant decrease in fasting plasma glucose (−15.61 ± 19.44 vs. −3.40 ± 24.78; p = .02), homeostatic model of assessment for insulin resistance (−1.17 ± 1.61 vs. −0.14 ± 1.64; p = .01), quantitative insulin sensitivity check index (0.01 ± 0.007 vs. 0.00 ± 0.01; p = .004), triacylglycerol (−22.30 ± 32.46 vs. −3.86 ± 30.57; p = .001), total cholesterol (−10.23 ± 10.36 vs. −2.03 ± 13.94; p = .004), low‐density lipoprotein cholesterol (LDL‐C; −8.15 ± 10.01 vs. −2.31 ± 9.37; p = .02), and LDL‐C/high‐density lipoprotein cholesterol (HDL‐C) ratio (−0.28 ± 0.37 vs. −0.08 ± 0.24; p = .01). No significant difference was observed between groups in HDL‐C, glycated hemoglobin, fasting insulin levels, and anthropometric measures. The present study suggests that okra consumption can elicit improvements in lipid profile, as well as glycemic markers, among T2D patients.
... Polysaccharides exert their hypoglycemic activity by increasing the plasma insulin levels and decreasing plasma sugar levels in mice (Hikino et al. 1985;Teng et al. 2011). Similarly, polysaccharides from G. lucidum inhibit hyperglycemia by regulating the expression of several key enzymes in the glucose metabolism pathway, such as hepatic glucokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, hepatic glycogen phosphorylase, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase, respectively (McCormack et al. 2001;Agius 2007;Xiao et al. 2012). A protein Ling Zhi-8 extracted from G. lucidum lowers plasma glucose concentrations and exhibits antitype 1 diabetes activity (Kino et al. 1989(Kino et al. , 1990. ...
Emergence of resistance in microorganisms against the current armamentarium of drugs along with severe side effects encountered with usage of synthetic drugs has resurrected natural products and herbal based drug industries. Among various sources of natural products, fungi have always been a key supplier of bioactive molecules of high medicinal importance. Over the years, fungi from the division Basidiomycota have been of keen interest due to isolation of putative bioactive compounds from them. The genus Ganoderma consists of wood-degrading polypore mushrooms which have been traditionally used in China and other Asian countries for the treatment of various ailments. Several species of genus Ganoderma exhibited anti-inflammatory, antitumor, antioxidant, antidiabetic, antiviral, antibacterial, antifungal, and immunomodulatory properties which are attributed to the presence of various bioactive compounds such as terpenoids, polysaccharides, steroids, fatty acids, and proteins in them. The aim of this chapter is to summarize the research progress on general pharmacological effects of Ganoderma.
... Of these, the polysaccharides (PSs) were identi ed as the major source for biological activity and therapeutic use [2][3][4]. PSs possess antitumor [5][6][7], immune-modulatory [6,8,9], antioxidant [10][11][12], and hypoglycemi [13] effects. Ganoderma-based drugs have been developed using these pharmaceutical properties. ...
Background
Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damage but also strengthen the muscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin (mSC) on satellite cells (SCs), which are known as the muscle stem cells.
Methods
The myogenic cells, included SCs (Pax7⁺) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridine assessed simultaneously. The molecular signal pathway was further investigated by using Western blotting and signal pathway inhibitors.
Results
Our results revealed that 200 µg/mL mSC had an optimal capability to significantly enhance the SC proliferation. Furthermore, this enhancement of SC proliferation was verified to be involved with activation of TAK1-JNK-AP-1 signaling pathway through TLR2, whose expression on SC surface was confirmed for the first time here.
Conclusion
Micronized sacchachitin extracted from GT was capable of promoting the proliferation of SC under a correct concentration.
... First diabetic group (each group has 8 mice) was treated with 50 mg/kg/d and second with 100 mg/kg/d. GLPs considerably reduced fasting serum glucose, insulin levels and epididymal fat/BW ratio with reference to diabetic control group in different doses [167]. Hot water and water-ether extracts of G. lucidum was administered orally to the mice in the different doses 60, 120 and 180 (mg/kg/day) for the duration of 2 weeks in hepatic injury. ...
... G. lucidum is a medicinal polypore mushroom widely used in traditional Chinese medicine with various pharmacological properties [12]. Xiao et al. found that 1-week treatment of polysaccharides in G. lucidum significantly attenuated hyperglycemia and the weight gain of adipose tissue in diabetic mice [28]. Consistently, we found that GDLP at both 100 and 400 mg/kg/day suppressed T2DM-induced body weight gain and the upregulation of blood glucose level in db/db mice. ...
BACKGROUND Type 2 diabetes mellitus (T2DM) and its comorbidities, including obesity, hypertension, and hyperlipidemia, are commonly associated with non-alcoholic fatty liver disease (NAFLD). Ganoderma lucidum polysaccharide (GDLP) is one of the central bioactive components in Ganoderma lucidum with anti-inflammatory, antioxidant, and hepatoprotective properties. However, the effect and mechanisms of GDLP in hepatic steatosis remain largely unknown. In the present study, we aimed to investigate the function of GDLP in hepatic steatosis and the underlying mechanism. MATERIAL AND METHODS In this study, male db/db mice were received with a high-fat diet (HFD) to investigate the effect of GDLP in T2DM-induced hepatic steatosis. The biological characteristics of the hepatic steatosis were evaluated through the detection of clinical indicators, including biochemical parameters, histopathology, and related cytokine levels. Additionally, the protein expression levels of Nrf2 (nuclear factor E2 (erythroid-derived 2)-related factor-2) signaling pathway were investigated by using western blotting and immunohistochemical staining. RESULTS The levels of food/water intake, body weight, fasting blood glucose, plasma lipids, urinary biomarkers, hepatic lipid accumulation, and tumor necrosis factor (TNF)-alpha were observably decreased in GDLP-treated db/db mice. Additionally, administration of GDLP increased the expression of various antioxidases, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), whereas it reduced the level of malonaldehyde (MDA). Furthermore, GDLP was significantly promoted protein expression level of Nrf2 and its downstream target gene HO-1 (heme oxygenase-1) while decreased TNF-alpha expression. CONCLUSIONS These results indicate that GDLP against T2DM-induced hepatic steatosis, oxidative stress, and inflammation by improving the Nrf2/HO-1 signaling pathway in db/db mice, suggesting the GDLP may serve as an effective strategy for in fatty liver treatment.
... Furthermore, preliminary studies on the potential antidiabetic effect was observed from the reduction of blood glucose under OGTT [47]. A more comprehensive study in this area is however required though the trend is similar with the antiobesity, antihyperlipidemic and antidiabetic effects of polysaccharides isolated from higher fungi like Ganoderma lucidum [79][80][81]. Associated with obesity and diabetes pathology is also the altered gut microbiota composition which other mushroom polysaccharides like those from G. lucidum have also been shown normalize [82,83]. ...
Dictyophora indusiata (Vent. Ex. Pers.) Fischer or Phallus indusiatus is an edible member of the higher mushroom phylum of Basidiomycetes. Known for its morphological elegance that gave it the names bridal veil fungus, veiled lady or queen of the mushrooms, it has numerous medicinal values that are beginning to be acknowledged through pharmacological efficacy studies. In an attempt to promote research on this valuable natural resource, the present communication aims to provide a comprehensive review of the chemistry, pharmacology and potential therapeutic applications of extracts and compounds isolated from D. indusiata. Of the bioactive compounds, the chemistry of the polysaccharides as major bioactive components primarily the β-(1 → 3)-D-glucan with side branches of β-(1 → 6)-glucosyl units are discussed, while small molecular weight compounds include terpenoids and alkaloids. Biochemical and cellular mechanisms of action from general antioxidant and anti-inflammatory to more specific signaling mechanisms are outlined along with potential applications in cancer and immunotherapy, neurodegenerative and chronic inflammatory diseases, etc. Further research areas and limitations of the current scientific data are also highlighted.
... Furthermore, preliminary studies on the potential antidiabetic effect was observed from the reduction of blood glucose under OGTT [47]. A more comprehensive study in this area is however required though the trend is similar with the antiobesity, antihyperlipidemic and antidiabetic effects of polysaccharides isolated from higher fungi like Ganoderma lucidum [79][80][81]. Associated with obesity and diabetes pathology is also the altered gut microbiota composition which other mushroom polysaccharides like those from G. lucidum have also been shown normalize [82,83]. ...
Dictyophora indusiata (Vent. Ex. Pers.) Fischer or Phallus indusiatus is an edible member of the higher mushroom phylum of Basidiomycetes. Known for its morphological elegance that gave it the names bridal veil fungus, veiled lady or queen of the mushrooms, it has numerous medicinal values that are beginning to be acknowledged through pharmacological efficacy studies. In an attempt to promote research on this valuable natural resource, the present communication aims to provide a comprehensive review of the chemistry, pharmacology and potential therapeutic applications of extracts and compounds isolated from D. indusiata. Of the bioactive compounds, the chemistry of the polysaccharides as major bioactive components primarily the β-(1 → 3)-D-glucan with side branches of β-(1 → 6)-glucosyl units are discussed, while small molecular weight compounds include terpenoids and alkaloids. Biochemical and cellular mechanisms of action from general antioxidant and anti-inflammatory to more specific signaling mechanisms are outlined along with potential applications in cancer and immunotherapy, neurodegenerative and chronic inflammatory diseases, etc. Further research areas and limitations of the current scientific data are also highlighted.
... In 2012, another polysaccharide was isolated from G. lucidum, which consists of glucose, mannose, xylose, arabinose, galactose, and ribose with a ratio of 68.45:15.87:4.71:4.08:3.78:3.11, respectively [30,44]. Xiao studied the effect of G. lucidum polysaccharides at 50 and 100 mg/kg/day administered for seven days to mice with streptozotocin-induced diabetes. ...
Pharmacotherapy using natural substances can be currently regarded as a very promising future alternative to conventional therapy of diabetes mellitus, especially in the case of chronic disease when the body is no longer able to produce adequate insulin or when it cannot use the produced insulin effectively. This minireview summarizes the perspectives, recent advances, and major challenges of medicinal mushrooms from Ganoderma genus with reference to their antidiabetic activity. The most active ingredients of those mushrooms are polysaccharides and triterpenoids. We hope this review can offer some theoretical basis and inspiration for the mechanism study of the bioactivity of those compounds.
... Xiao and colleagues (2012) investigated hypoglycemic effects and mechanism actions of G. lucidum polysaccharides (GLPs) in type 2 diabetic mice treated for seven days. GLPs-treated mice showed diminished levels of fasting serum glucose accompanied by reduced mRNA expression of hepatic glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and PEPCK ( Table 2), further indicating an intense action of G. lucidum in modulating gluconeogenesis/glycogenolysis key regulatory enzymes [145]. Likewise, F31 a predominant β-heteropolysaccharide present GLP has been reported to down-regulate glucose regulatory enzymes in the liver of diabetic mice via an AMPK-dependent mechanism ( Table 2) [146]. ...
Aging and aging-associated diseases are issues with unsatisfactory answers in the medical field. Aging causes important physical changes which, even in the absence of the usual risk factors, render the cardiovascular system prone to some diseases. Although aging cannot be prevented, slowing down the rate of aging is entirely possible to achieve. In some traditional medicine, medicinal herbs such as Ginseng, Radix Astragali, Ganoderma lucidum, Ginkgo Biloba, and Gynostemma pentaphyllum are recognized by the “nourishing of life,” and their role as anti-aging phytotherapeutics is increasingly gaining attention. By mainly employing PubMed here we identify and critically analysed 30 years of published studies focusing on the above herb’s active components against aging and aging-associated conditions. Although many plant-based compounds appear to exert an anti-aging effect, the most effective resulted in being flavonoids, terpenoids, saponins, and polysaccharides, which include astragaloside, ginkgolide, ginsenoside, and gypenoside specifically covered in this review. Their effects as anti-aging factors, improvers of cognitive impairments, and reducers of cardiovascular risks are described, as well as the molecular mechanisms underlying the above-mentioned effects along with their potential safety. Telomere and telomerase, PPAR-α, GLUTs, FOXO1, caspase-3, bcl-2, along with SIRT1/AMPK, PI3K/Akt, NF-κB, and insulin/insulin-like growth factor-1 pathways appear to be their preferential targets. Moreover, their ability to work as antioxidants and to improve the resistance to DNA damage is also discussed. Although our literature review indicates that these traditional herbal medicines are safe, tolerable, and free of toxic effects, additional well-designed, large-scale randomized control trials need to be performed to evaluate short- and long-term effects and efficacy of these medicinal herbs.
... Ganoderma lucidum (GL), as a famous herbal medicine in China and Japan more than 2000 years, has been prized for its medicinal vitality such as promoting longevity and benefiting for general health [1,2]. Especially, GL polysaccharides (GLPs) are a major bioactive ingredient and has been identified that it has regulatory abilities in most of physiological progress, including antitumor effects, immune modulation, significant antioxidant activity, and hypoglycaemic [3][4][5][6][7][8]. Recently, the GLPs has been extracted and purified to be applied in health-promoting as medications or dietary supplements [9]. ...
Ganoderma lucidum polysaccharides (GLPs) are commonly used as health-promoting medicine and dietary supplement due to the positive effects in immune modulation, antitumor and antioxidant activities. However, whether GLPs executes other uncharacterized effects is largely unclear. The rats were pre-primed with GLPs and then administrated with canonical "cocktail probes" of cytochrome P450 (CYP450) isozymes including caffeine, tolbutamide, dextromethorphan, omeprazole, and midazolam. The plasma concentrations of probes at each indicated time point were simultaneously detected using the designed high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. The results suggested that GLPs could increase the accumulated levels of caffeine, tolbutamide and midazolam in plasma as compared to control group. Besides, GLPs reduced the concentration of dextromethorphan in blood at high dose, while elevated it at low dose. GLPs could inhibit the activities of CYP1A2, and CYP3A4, additionally; GLPs at low dose suppressed the activity of CYP2D6, which demonstrated that drugs co-administrated with GLPs might require strictly evaluating the dose relation.
Ethnopharmacological relevance:
As a kind of traditional medicinal fungi, Ganoderma lucidum has been employed as folk medicine in China against multiple metabolic diseases on account of its superior bioactivities. Recently, accumulated reports have investigated the protective effects of G. lucidum polysaccharides (GLP) on ameliorating dyslipidemia. However, the specific mechanism by which GLP improves dyslipidemia is not completely clear.
Aims of the study:
This study aimed to investigate the protective effects of GLP on high-fat-diet induced hyperlipidemia and exploring its underlying mechanism.
Materials and methods:
The GLP was successfully obtained from G. lucidum mycelium. The mice were conducted with high-fat-diet to establish the hyperlipidemia model. Biochemical determination, histological analysis, immunofluorescence, western blot and real-time qPCR were used to assess the alterations in high-fat-diet-treated mice after the GLP intervention.
Results:
It was found that GLP administration significantly decreased body weight gain and the excessive lipid levels, and partly alleviated tissue injury. Oxidative stress and inflammations were efficiently ameliorated after the treatment of GLP by activing Nrf2-Keap1 and inhibiting NF-κB signal pathways. GLP promoted cholesterol reverse transport by LXRα-ABCA1/ABCG1 signaling, increased the expressions of CYP7A1 and CYP27A1 responsible for bile acids production, accompanied by inhibition of intestinal FXR-FGF15 levels. Besides, multiple target proteins involved in lipid metabolism were also significantly modulated under the intervention of GLP.
Conclusion:
Taken together, our results suggested that GLP showed potential lipid-lowering effects and its possible mechanism was involved in improving oxidative stress and inflammation response, modulating bile acids synthesis and lipid regulatory factors, and promoting reverse cholesterol transport, thereby suggesting that GLP may possibly used as a dietary supplement or medication for the adjuvant therapy for hyperlipidemia.
Background:
Novel functional polysaccharides from fungi are important nutraceuticals for food applications. A purified exopolysaccharide (MEP 2) was extracted and purified from the fermentation liquor of Morchella esculenta. The aim of this study was to investigate the digestion profile, antioxidant abilities and effect on the microbiota composition in diabetic mice of MEP 2.
Results:
MEP 2 is stable during in vitro saliva digestion but partially degraded during gastric digestion. The digest enzymes exert negligible effect on the chemical structure of MEP 2. Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. After digestion, the antioxidant ability increases as revealed by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. Both MEP 2 and its digested components show strong α-amylase and moderate α-glucosidase inhibition activities, leading us to further investigate its ability to modulate the diabetic symptoms. MEP 2 treatment ameliorate the inflammatory cell infiltration and increase the size of pancreas inlets. Serum concentration of HbA1c was significantly reduced. Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. MEP 2 increases the diversity of gut microbiota and modulate the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina and several Lachnospiraceae species.
Conclusion:
MEP 2 was partially degraded during the in vitro digestion. Its potential antidiabetic bioactivities may associate with its α-amylase inhibition and gut microbiome modulation ability. This article is protected by copyright. All rights reserved.
Edible fungus are widely eaten because of their delicious taste and high nutritional value. Growing evidence indicates that edible fungus are rich in various active ingredients including polysaccharides, proteins, fats, vitamins, and other ingredients. Polysaccharide is one of the main active ingredients of edible fungi. Increasing researches have confirmed that edible fungus polysaccharides (EFPs) showed multiple biological activities such as antioxidant, anti‐inflammatory, anti‐tumor, immune regulation, anti‐virus, gut microbiota regulation, hypoglycemic, etc. Hence, EFPs related researches have received more and more attention due to their non‐toxic, high medical and nutritional values. This paper reviews the latest research progress of EFPs biological activities, and looks forward to their future development trend. This review provides a theoretical basis for studying the application of EFPs in the fields of biomedicine, cosmetics, and health food, and promotes the development and utilization of EFPs. This article is protected by copyright. All rights reserved
In this paper, we reported an excellent hypoglycemic effect of a Ganoderma lucidium polysaccharide F31 with efficacies between 45 and 54 %, approaching to that of liraglutide (52 %). Significantly, F31 reduced the body weight gains and food intakes. F31 decreased 4 key compounds, consisting of adenosine, adenosine, galactitol and glycerophosphocholine and elevated 8 key compounds, including arginine, proline, arachidonic acid, creatine, aspartic acid, leucine, phenylalanine and ornithine, which protected kidney function. Also, apoptosis was promoted by F31 in epididymal fat through increasing Caspase-3, Caspase-6 and Bax and decreasing Bcl-2. On 3 T3-L1 preadipocyte cells, F31 induced early apoptosis through reducing mitochondrial membrane potential. Finally, a molecular docking was performed to reveal a plausible cross-talk between kidney and epididymal fat through glycerophosphorylcholine-Bax axis. Overall, F31 alleviated hyperglycemia through kidney protection and adipocyte apoptosis in db/db mice. This work may provide novel insights into the hypoglycemic activity of polysaccharides.
Chronic diseases have drawn much attention as the primary cause of death and disability. In exploring novel side-effect-free agents against chronic diseases, significant efforts have been devoted to mushroom polysaccharides due to their diverse biological activities. This work reviewed the structural features, biological performances and molecular mechanisms of mushroom polysaccharides in managing cancers, diabetes mellitus and cardiovascular diseases. The potentials of mushroom polysaccharides against chronic diseases highly depend on their structural features, including monosaccharide composition, molecular weight, the type and configuration of glycosidic bonds, degree of branching, the type of substituent pattern and chain conformation. Regarding their working mechanisms, shared and disease-specific pathways were found. The three chronic diseases shared the regulation of specific signalling pathways and the adjustment of gut microbiota. In addition, the roles of transcription factors, receptors, enzymes, hormones and other functional proteins involved in the molecular mechanisms of mushroom polysaccharides against chronic diseases are first elaborated herein. The present review describes the state of the art of mushroom polysaccharides in treating chronic diseases and addresses the perspectives, and will further promote research on this topic.
Diabetes mellitus (DM) is a metabolic disorder disease, and the number of diabetic patients will reach 578 million by 2030 predictably. Currently, 8 classes of small molecular drugs are used for treating diabetes. However, these drugs cannot completely meet patients’ needs, due to diabetic complications need to be addressed along with diabetes, such as nephropathy, and cardiovascular diseases. Besides, more types of drugs need to be provided for more choices. Hence, scientists still seek lead compounds with hypoglycemic effects. Natural products (NPs) are a reservoir of diverse structures and bioactivities with low toxicity and less side effects. And some of them show effects on diabetic complications, which is a significant idea for drug development. This review aims to summarize natural products with hypoglycemic effects and their details, such as potential mechanisms, biological data, and particularly their advantages in treating diabetes. Considering the huge number of NPs was reported with anti-diabetic activity, and some of them need to be re-validated, this review focuses on the bioactive compounds with in vivo activities. In the end, the trend of natural products treating diabetes was discussed. We hope this review provide a comprehensive and convincing summary, thus lending support to anti-diabetic natural products research.
Neutral polysaccharides (NHSPs) from the mushroom Hohenbuehelia serotina were purified by D301/D152 resin ion-exchange chromatography and DEAE-cellulose anion exchange chromatography. The weight-average molecular weight (MW) and number-average molecular weight (Mn) of NHSP were 1,821 and 820.55 kDa, respectively. A monosaccharide component analysis showed that NHSP was composed of glucose, galactose, and mannose in molar ratio 2.6:2.1:1.0. FT-IR and NMR (1H and HSQC) spectroscopic analyses revealed that NHSP contained mainly 1,3-linked β-D-glucose, 1,4-linked β-D-glucose, 1,6-linked β-D-mannose, 1,6-linked α-D-mannose, and 1,6-linked β-D-galactose. The thermogravimetric analysis (TGA) showed that NHSP has good thermal stability below 250°C. NHSP notably reduced the blood glucose level (hypoglycemic effect) at dose 200 mg/kg for 21 days in a type 2 diabetic mouse model. NHSP reduced the liver index significantly, suggesting that it may help prevent hepatic steatosis or hepatomegaly.
In order to improve the utilization value of sweet corn cobs, we extracted a new non‐starch polysaccharide from sweet corn cobs and named SCP‐80‐I. It showed that SCP‐80‐I was a neutral homogeneous polysaccharide composed of glucose with a molecular weight of 175.453 kDa. We also explore the structural features of SCP‐80‐I and we found that it possessed a backbone of →4‐Glc‐1→4‐Glc‐1→4,6‐Glc‐1→4‐Glc‐1→, and the branched chain was →6‐Glc‐1→ linked to the main chain through O‐6 of →4,6‐Glc‐1→. We predicted that SCP‐80‐I may have a function of anti‐oxidation and hypoglycemic due to its structure. This study provides some reference value for sweet corn cob polysaccharides in the creation of functional food.
Recently available drugs of synthetic origin in management of obesity and diabetes are costly and not affordable by poor people and have potential adverse side effects, and thereby these cause serious other complications among many obese and diabetic patients. As a result, some of these drugs have been withdrawn from the market. For this reason, most of the leading pharmaceutical industries have paid their attention for discovery of potential natural compounds with low-cost and minimal adverse effects for treatment of obesity and diabetes as an alternative strategy. In the earlier chapter, we have discussed that a large variety of natural resources, namely, dietary fruits, vegetables, grains, plants, seaweeds, edible and medicinal mushrooms, marine fishes and cucumbers, and microorganisms, have potential anti-obesity and antidiabetic effects. Their bioactive phytochemicals having diverse skeletal structures and belonging to different chemical classes, such as flavonoids, simple phenolics, lignans, stilbenoids, curcuminoids, tannins, alkaloids, terpenoids, steroids, saponins, organosulfurs, thiosugars, and polysaccharides. A growing body of evidence demonstrates that these natural products have multiple targets of action for prevention and treatment of obesity and diabetes. Most of these natural components exhibit hypolipidemic, hypoglycemic, antioxidant, and anti-inflammatory activities for improvement of insulin resistance, insulin secretion, and insulin action in insulin-responsive tissues for amelioration of lipid and glucose metabolic disorders in cellular and vivo models of obesity and diabetes. In this chapter, we address the pharmacology of some phytochemicals having potent anti-obesity and antidiabetic activity and their major natural sources and molecular targets.
The impact of modification in molecules or deacetylation of konjac glucomannan (KGM) on the stress resistance in vivo has rarely been studied systematically. This research studied the effects of KGM with different molecular weights and degrees of deacetylation on the stress resistance and physical fitness of Caenorhabditis elegans. After the nematodes were incubated with different modified KGM, the survival rate of nematodes under oxidative and heat stress, as well as the fertility and locomotion were measured. KGM(2-5) can significantly prolong the mean and maximum lifespan of nematodes in the presence of paraquat. Under heat stress, all partially degraded konjac glucomannan (PDKGM) showed the significant extension of survival rates. Da(1-3) improved the survival rates of nematodes under oxidative stress. Furthermore, genes expression showed that KGM(2-5) and Da(1-3) upregulated the expression of sod-3, hsp-16.2, and atf-7. Taken together, molecular weight reduction or deacetylation of KGM have a significant impact on the stress resistance in vivo. PDKGM applied in stress resistance will be suggested not to exceed 200 kDa and deacylation of KGM will be suggested to be below 50%.
Ganoderma lucidum is known in China and Japan as Ling-Zhi and Reishi. Due to medicinal properties and different nutritional compositions, ganoderma lucidum is currently used in food products. It contains essential fatty acids, essential amino acids, and a wide range of polysaccharides; all of which seem to be effective in lowering blood sugar level. This study aims to review the anti-diabetic and hypoglycemic effects of various powders, extracts, and components of ganoderma lucidum, by searching articles in Persian and English published from 2001 to 2020 in SID, MagIran, Scopus, PubMed, Web of Science and Google Scholar databases using the keywords: Active compounds, ganoderma lucidum, diabetes mellitus, hyperglycemia. The results showed that ganoderma lucidum uptake in most cases reduced fasting blood sugar, glycosylated hemoglobin, and insulin resistance in diabetic patients due to the its active compounds including the extracted polysaccharides, proteins and triterpenoids. Moreover, its antioxidant and anti-inflammatory properties seems to reduce the complications of diabetes. In conclusion, the consumption of ganoderma lucidum in diabetic patients can be effective in controlling and preventing the disease, although more studies are needed on its effective dose, side effects and toxicity in human samples.
With the advent of the aging society, how to grow old healthily has become an important issue for the whole of society. Effective intervention strategies for healthy aging are most desired, due to the complexity and diversity of genetic information, it is a pressing concern to find a single drug or treatment to improve longevity. In this study, long-term administration of triterpenoids of Ganoderma lucidum (TGL) can mitigate brain physiological decline in normal aging mice. In addition, the age-associated pathological features, including cataract formation, hair loss, and skin relaxation, brown adipose tissue accumulation, the β-galactosidase staining degree of kidney, the iron death of spleen, and liver functions exhibit improvement. We used the APP/PS1 mice and 3 × Tg-AD mice model of Alzheimer’s Disease (AD) to further verify the improvement of brain function by TGL and found that Ganoderic acid A might be the effective constituent of TGL for anti-aging of the brain in the 3 × Tg-AD mice. A potential mechanism of action may involve the regulation of sphingolipid metabolism, prolonging of telomere length, and enhance autophagy, which allows for the removal of pathological metabolites.
Our team previously demonstrated that Ganoderma lucidum spores (GLS) and resistant starch (RS) had hypoglycemic effects separately on type 2 diabetic mellitus (T2DM) rats. This work was to explore the effects of administering encapsulated GLS within RS (referred to as EGLS) in the T2DM rats, which were induced by streptozotocin (STZ). The EGLS was orally administered to rats for 28 days. The parameters of glycometabolism and lipometabolism were evaluated, and fecal microbiota composition was investigated. The results showed that EGLS significantly enhanced glycometabolism and lipometabolism parameters in T2DM rats, which might be associate with the enhancement of the glucose and lipid metabolism, insulin secretion, and glycogen synthesis and reduced lipogenesis. Furthermore, the intervention of EGLS also reduced the Proteobacteria community and improved dysfunctional gut microbiota. This study indicated EGLS may be a potential candidate for dietary intervention to modulate diabetes.
Four new types of water‐soluble polysaccharides were isolated from Cardamine hupingshanensis. Herein, we examine C. hupingshanensis polysaccharide No. 2 (CHP‐2) with a molecular weight of 21.75 kDa. Analysis revealed that CHP‐2 is composed of D‐glucuronic acid, D‐galacturonic acid, glucose, galactose, and L‐arabinose. It was speculated that the main connecting bond was →4)‐α‐D‐Glc(p)‐(1→), →t)‐α‐D‐Glcp‐(1→). Through perfusion experiments using streptozotocin‐induced diabetic rats, oral CHP‐2 solution was found to significantly reduce food intake, water intake, and fasting blood glucose levels, while increasing the weights of rats. In addition, CHP‐2 significantly reduces the serum and liver malondialdehyde contents and increases the activity of the corresponding antioxidant enzymes. Moreover, the effect elicited by the CHP‐2 solution was similar to that of phenformin hydrochloride solution. Hence, the results of this study suggest that CHP‐2 exhibits blood sugar‐lowering and anti‐oxidation effects.
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Previous research has shown that the extracts from the Ganoderma lucidum spore (GS) have potentially cardioprotective effects, but there is still abundant room for development in determining its mechanism. In this study, the rat model of cardiac dysfunction was established by intraperitoneal injection of trimethylamine‐N‐oxide (TMAO), and the extracts of GS (oil, lipophilic components, and polysaccharides) were given intragastrically at a dose of 50 mg/kg/day to screen the pharmacological active components of GS. After 50 days of treatments, we found that the extraction from GS reduced the levels of total cholesterol, triglyceride, and low‐density lipoprotein; increased the levels of high‐density lipoprotein; and reduced the levels of serum TMAO when compared to the model group (P < 0.05); especially the GS polysaccharides (DT) and GS lipophilic components (XF) exhibited decreases in serum TMAO compared to TMAO‐induced control. The results of 16S rRNA sequencing showed that GS could change the gut microbiota, increasing the abundance of Firmicutes and Proteobacteria in the DT‐treated group and XF‐treated group, while reducing the abundance of Actinobacteria and Tenericutes. Quantitative proteomics analysis showed that GS extracts (DT and XF) could regulate the expression of some related proteins, such as Ucp1 (XF‐TMAO/M‐TMAO ratio is 2.76), Mpz (8.52), Fasn (2.39), Nefl (1.85), Mtnd5 (0.83), Mtnd2 (0.36), S100a8 (0.69), S100a9 (0.70), and Bdh1 (0.72). The results showed that XF can maintain the metabolic balance and function of the heart by regulating the expression of some proteins related to cardiovascular disease, and DT can reduce the risk of cardiovascular diseases by targeting gut microbiota.
Diabetes mellitus is a chronic metabolic disorder that occurs when the pancreas is no longer able to make insulin or the body is not able to make use of the insulin. Diabetes mellitus affects people from developed as well as developing countries. According to the International Diabetic Federation 2017 report, there is tremendous increase in number of diabetic people throughout the world from last few decades. The total number had reached 327 million in the year 2017. High prevalence, complex pathogenesis and rapidly developing complications result in an urge in the need of an effective treatment against diabetic progression.
Diabetes mellitus (DM) is a metabolic disorder with a rising prevalence globally. Currently about 400 million people are affected. In 2016, it was the seventh leading cause of death worldwide. Diabetes mellitus is prevalent in most countries. Its major feature is the high level of blood glucose which can be caused by insulin resistance or reduced insulin production. As the disease progresses, complications like diabetic neuropathy, nephropathy, and retinopathy occur. The use of herbs and natural products in the management of diabetes mellitus dates to the prehistoric era. Eighteen studies from about nine countries showed that between 18% and 72% use traditional and complementary medicine in the management of diabetes. In developing countries where the disease is highly prevalent natural products are very common because of ready availability, cheapness, and minimal side effects. This review highlights alkaloids, one of the most important secondary metabolites isolated from plants which have been studied to have anti-diabetes effects. Alkaloids are a group of highly diverse natural products that contain one or more basic nitrogen atoms in a heterocyclic ring. The various plants that contain them, their pharmacological actions studied thus far, mechanism of action will be extensively discussed. The aim of this review is to provide rich knowledge on research carried out thus far on plant alkaloids in the management of diabetes: their pharmacology, chemistry, and effectiveness which will serve as a platform for further research and development of novel drug molecules that can further help in the management of this disease.
Type 2 diabetes mellitus (T2DM) is an endocrine and metabolic disease with insulin resistance and insulin deficiency, and the structural changes of gut microbiota play a very important role in the occurrence and development of T2DM. Gut microbiota is an important part of intestinal micro-ecosystem. Long-term high-sugar and high-fat diet can change the intestinal microenvironment, especially the structure of gut microbiota. Gut bacteria affect the body’s absorption of sugars and energy, as well as regulating the production of lipopolysaccharide and short-chain fatty acid. The changes of gut microbiota can induce low-grade chronic inflammation, affect bile acid metabolism, and lead to destruction and apoptosis of islet cells and insulin resistance. It is noteworthy that natural polysaccharides have been widely used in regulating gut microbiota with many advantages, such as good stability, nontoxicity, and safety. Thus, polysaccharide-regulated composition changes of gut microbiota have become a new target for prevention and treatment of type 2 diabetes.
Background: Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damagebut also strengthen themuscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin(mSC) on satellite cells (SCs), which are known as the muscle stem cells.
Methods: The myogenic cells, included SCs (Pax7 +) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridineassessed simultaneously. The molecular signal pathway was further investigated by using Western blotting and signal pathway inhibitors.
Results: Our results revealed that 200 µg/mL mSC had an optimal capability to significantly enhance the SC proliferation. Furthermore, this enhancement of SC proliferation was verified to be involved with activation of TAK1-JNK-AP-1 signaling pathway through TLR2, whose expression on SC surface was confirmed for the first time here. Conclusion: Micronized sacchachitinextracted fromGT was capable of promoting the proliferation of SC under a correct concentration.
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.
As extracts from Ganoderma lucidum (G. lucidum, Lingzhi) have been reported to be an alternative adjuvant treatment for diabetes, numerous of work have been carried out on it. Among the many biologically active constituents of Ganoderma, polysaccharides, proteoglycans, proteins, and triterpenoids have been shown to have hypoglycemic effects. Based on our research and other references, this article discusses the antidiabetic effect of Ganoderma mediated by protecting pancreas islet; inhibiting protein tyrosine phosphatase 1B, a promising therapeutic target of diabetes; decreasing lymphocyte infiltration; and increasing the antibody detection of insulin in diabetic mice. This review summarizes researches about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins, and triterpenoids from Ganoderma as a guide for future research on diabetes and its complications. In addition, clinical studies with diabetic indexes are reviewed.
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Mushrooms are macroscopic fungi which can be either epigeous or hypogeous and is estimated to be 140,000 on earth, yet only 10% are known. Since ancient time, it played a diverse role in human history for mycolatry, mycophagy and as medicine in folklore and religion. Many Asian and western countries consider mushrooms as panacea for a large number of diseases and utilized for consumption as a gourmet food for its taste as well as flavor. In recent years, scientific research fraternities have confirmed that various extracts and metabolites of mushrooms used traditionally are able to treat a wide range of diseases due to their balanced modulation of multiple targets thereby providing a greater therapeutic effect or equivalent curative effect to that of modern medicine. Medicinal mushrooms especially those belonging to higher basidiomycete groups are reservoir of bioactive compounds with multiple therapeutic properties. The present review provides historical importance as well as an updated information on pharmacologically relevant higher basidiomycetes belong to the genus Agaricus, Auricularia, Phellinus, Ganoderma, Pleurotus, Trametes and Lentinus and their biologically active secondary metabolites. This will help the researchers to understand various type of secondary metabolites, their therapeutic role and related in vivo or in vitro work at a glance. The mounting evidences from several scientific community across the globe, regarding various therapeutic applications of mushroom extracts, unarguably make it an advance research area worth mass attention.
Polysaccharide from Ganoderma lucidum is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel G. lucidum polysaccharide‑chromium (III) [GLP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GLP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 5.71 mg/mL, pH 6.36, temperature 66.4 °C and time 2.0 h, respectively. The pH was the most significant factor, followed by reaction temperature and CrCl3 concentration. Under the optimal conditions, the experimental chelation rate was 94.17 ± 1.0% for GLP-Cr(III) complex, which agreed closely with the predicted value (94.60%). Fourier transform infrared (FT-IR) spectroscopy revealed that the primary sites of chromium (III)-binding in G. lucidum polysaccharide were OH and CO groups, which induce the morphology change from flat sheet to rough surface. Meanwhile, according to the result of X-ray diffraction (XRD), the crystal degree of GLP was disappeared after chelation with Cr(III). The presence of a "blind zone" in the 1H NMR spectrum obviously indicated the binding of Cr(III) to GLP. Additionally, the effects of GLP-Cr(III) complex on hyperglycemia and hyperlipidemia in high fructose and fat diet-induced pre-diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in mice supplemented with GLP-Cr(III) complex (50 mg/kg day) were significantly lower than the model group (P < 0.01). More importantly, the GLP-Cr(III) complex had no significant adverse effects on the physiological metabolism, organ index, and liver tissue morphology of mice fed a normal diet. These results suggest that GLP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.
This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal mushroom Phellinus caryophylli (Racib.) G. Cunn. (PCE) against acetaminophen (APAP)-induced hepatotoxicity in Swiss albino mice. The mice orally received APAP (150 mg/kg body weight), followed by PCE extract (250 or 500 mg/kg body weight). The liver damage induced by APAP was analyzed on the basis of blood serum parameters (glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, and alkaline phosphatase), antioxidant assays (reduced glutathione and glutathione peroxidase), and tissue peroxidation based on malondialdehyde level. The molecular mechanism underlying the prevention of APAP-induced damage by PCE was also analyzed. Liver damage was confirmed on the basis of increased serum parameter values, decreased antioxidant levels, and cellular and molecular alterations, which PCE restored in a dose-dependent manner. At a transcriptional level, PCE downregulated expression of the preapoptototic gene Bax and the inflammatory gene Cox2 but upregulated the antiapoptotic gene Bcl2 in the mice that received APAP. PCE exerted a hepatoprotective effect by preventing apoptotic and inflammatory events caused by APAP. Thus, this study demonstrates a hepatoprotective effect of PCE, which could be explored further for managing hepatopathy.
We conducted a survey to know the prevalence of diabetes and obesity in young-adult (20-40 years) men and non-pregnant-women in Kashmir Valley (India); prevalence of latter is presented here. The age-adjusted prevalence of overweight-obesity was 16.3% and that of obesity 5.1%; the relationship of overweight-obesity with glucose intolerance is discussed.
Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is attributed to increased hepatic gluconeogenesis, which has been ascribed to increased transcriptional expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, catalytic (G6Pc). To test this hypothesis, we examined hepatic expression of these 2 key gluconeogenic enzymes in 2 rodent models of fasting hyperglycemia and in patients with T2DM. In rats, high-fat feeding (HFF) induces insulin resistance but a robust beta-cell response prevents hyperglycemia. Fasting hyperglycemia was induced in the first rat model by using nicotinamide and streptozotocin to prevent beta-cell compensation, in combination with HFF (STZ/HFF). In a second model, control and HFF rats were infused with somatostatin, followed by portal vein infusion of insulin and glucagon. Finally, the expression of these enzymes was measured in liver biopsy samples obtained from insulin sensitive, insulin resistant, and untreated T2DM patients undergoing bariatric surgery. Rats treated with STZ/HFF developed modest fasting hyperglycemia (119 +/- 4 vs. 153 +/- 6 mg/dL, P < 0.001) and increased rates of endogenous glucose production (EGP) (4.6 +/- 0.6 vs. 6.9 +/- 0.6 mg/kg/min, P = 0.02). Surprisingly, the expression of PEPCK or G6Pc was not increased. Matching plasma insulin and glucagon with portal infusions led to higher plasma glucoses in the HFF rats (147 +/- 4 vs. 161 +/- 4 mg/dL, P = 0.05) with higher rates of EGP and gluconeogenesis. However, PEPCK and G6Pc expression remained unchanged. Finally, in patients with T2DM, hepatic expression of PEPCK or G6Pc was not increased. Thus, in contrast to current dogma, these data demonstrate that increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with T2DM.
We used the perfused hemicorpus preparation to measure individual rates of protein synthesis and degradation. Using fed animals, perfused either with or without insulin, muscle protein synthesis and hemicorpus protein degradation rates were similar, but myofibrillar protein degradation was clearly increased in the uremic preparations. When the animals were fasted, differences in the rates of skeletal muscle protein turnover were apparent. Uremic rats lost more wt at both 24 and 48 hr of fasting when compared to either ad libitum fed or pair-fed controls who started fasting at body wts equivalent to our uremic rats. The accelerated wt loss was accompanied by lower rates of protein synthesis, higher degradation rates, and greater net protein catabolism in our uremic rats. Alterations in body lipid content were present in uremia and correlated with the rate of protein degradation in both control and uremic rats. These data demonstrated that even in the fed state, uremia is associated with subtle alterations in skeletal muscle protein turnover. When stressed, these alterations become more pronounced. Insufficient stores of body lipids, either due to inadequate nutrition or altered metabolism, may contribute to the alterations in muscle protein turnover seen in chronic renal insufficiency.
We previously showed that angiotensin II (ang II) infusion in the rat produces cachexia and decreases circulating insulin-like growth factor I (IGF-I). The weight loss derives from an anorexigenic response and a catabolic effect of ang II. In these experiments we assessed potential catabolic mechanisms and the involvement of the IGF-I system in these responses to ang II. Ang II infusion caused a significant decrease in body weight compared with that of pair-fed control rats. Kidney and left ventricular weights were significantly increased by ang II, whereas fat tissue was unchanged. Skeletal muscle mass was significantly decreased in the ang II-infused rats, and a reduction in lean muscle mass was a major reason for their overall loss of body weight. In skeletal muscles, ang II did not significantly decrease protein synthesis, but overall protein breakdown was accelerated; inhibiting lysosomal and calcium-activated proteases did not reduce the ang II-induced increase in muscle proteolysis. Circulating IGF-I levels were 33% lower in ang II rats vs. control rats, and this difference was reflected in lower IGF-I messenger RNA levels in the liver. Moreover, IGF-I, IGF-binding protein-3, and IGF-binding protein-5 messenger RNAs in the gastrocnemius were significantly reduced. To investigate whether the reduced circulating IGF-I accounts for the loss in muscle mass, we increased circulating IGF-I by coinfusing ang II and IGF-I, but this did not prevent muscle loss. Our data suggest that ang II causes a loss in skeletal muscle mass by enhancing protein degradation probably via its inhibitory effect on the autocrine IGF-I system.
The ability of insulin to suppress gluconeogenesis in type II diabetes mellitus is impaired; however, the cellular mechanisms for this insulin resistance remain poorly understood. To address this question, we generated transgenic (TG) mice overexpressing the phosphoenolpyruvate carboxykinase (PEPCK) gene under control of its own promoter. TG mice had increased basal hepatic glucose production (HGP), but normal levels of plasma free fatty acids (FFAs) and whole-body glucose disposal during a hyperinsulinemic-euglycemic clamp compared with wild-type controls. The steady-state levels of PEPCK and glucose-6-phosphatase mRNAs were elevated in livers of TG mice and were resistant to down-regulation by insulin. Conversely, GLUT2 and glucokinase mRNA levels were appropriately regulated by insulin, suggesting that insulin resistance is selective to gluconeogenic gene expression. Insulin-stimulated phosphorylation of the insulin receptor, insulin receptor substrate (IRS)-1, and associated phosphatidylinositol 3-kinase were normal in TG mice, whereas IRS-2 protein and phosphorylation were down-regulated compared with control mice. These results establish that a modest (2-fold) increase in PEPCK gene expression in vivo is sufficient to increase HGP without affecting FFA concentrations. Furthermore, these results demonstrate that PEPCK overexpression results in a metabolic pattern that increases glucose-6-phosphatase mRNA and results in a selective decrease in IRS-2 protein, decreased phosphatidylinositol 3-kinase activity, and reduced ability of insulin to suppress gluconeogenic gene expression. However, acute suppression of HGP and glycolytic gene expression remained intact, suggesting that FFA and/or IRS-1 signaling, in addition to reduced IRS-2, plays an important role in downstream insulin signal transduction pathways involved in control of gluconeogenesis and progression to type II diabetes mellitus.
The objective of the present study was to develop a rat model that replicates the natural history and metabolic characteristics of human type 2 diabetes and is also suitable for pharmacological screening. Male Sprague-Dawley rats (160-180 g) were divided into two groups and fed with commercially available normal pellet diet (NPD) (12% calories as fat) or in-house prepared high-fat diet (HFD) (58% calories as fat), respectively, for a period of 2 weeks. The HFD-fed rats exhibited significant increase in body weight, basal plasma glucose (PGL), insulin (PI), triglycerides (PTG) and total cholesterol (PTC) levels as compared to NPD-fed control rats. Besides, the HFD rats showed significant reduction in glucose disappearance rate (K-value) on intravenous insulin glucose tolerance test (IVIGTT). Hyperinsulinemia together with reduced glucose disappearance rate (K-value) suggested that the feeding of HFD-induced insulin resistance in rats. After 2 weeks of dietary manipulation, a subset of the rats from both groups was injected intraperitoneally with low dose of streptozotocin (STZ) (35 mg kg(-1)). Insulin-resistant HFD-fed rats developed frank hyperglycemia upon STZ injection that, however, caused only mild elevation in PGL in NPD-fed rats. Though there was significant reduction in PI level after STZ injection in HFD rats, the reduction observed was only to a level that was comparable with NPD-fed control rats. In addition, the levels of PTG and PTC were further accentuated after STZ treatment in HFD-fed rats. In contrast, STZ (35 mg kg(-1), i.p.) failed to significantly alter PI, PTG and PTC levels in NPD-fed rats. Thus, these fat-fed/STZ-treated rats simulate natural disease progression and metabolic characteristics typical of individuals at increased risk of developing type 2 diabetes because of insulin resistance and obesity. Further, the fat-fed/STZ-treated rats were found to be sensitive for glucose lowering effects of insulin sensitizing (pioglitazone) as well as insulinotropic (glipizide) agents. Besides, the effect of pioglitazone and glipizide on the plasma lipid parameters (PTG and PTC) was shown in these diabetic rats. The present study represents that the combination of HFD-fed and low-dose STZ-treated rat serves as an alternative animal model for type 2 diabetes simulating the human syndrome that is also suitable for testing anti-diabetic agents for the treatment of type 2 diabetes.
This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly.
Fasting hyperglycemia, a prominent finding in diabetes, is primarily due to increased gluconeogenesis. The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a possible therapeutic target in insulin-resistant states. Synthetic, optimized antisense oligonucleotides (ASOs) specifically inhibit Foxo1 expression. Here we show the effect of such therapy on insulin resistance in mice with diet-induced obesity (DIO). Reducing Foxo1 mRNA expression with ASO therapy in mouse hepatocytes decreased levels of Foxo1 protein and mRNA expression of PEPCK by 48 +/- 4% and G6Pase by 64 +/- 3%. In mice with DIO and insulin resistance, Foxo1 ASO therapy lowered plasma glucose concentration and the rate of basal endogenous glucose production. In addition, Foxo1 ASO therapy lowered both hepatic triglyceride and diacylglycerol content and improved hepatic insulin sensitivity. Foxo1 ASO also improved adipocyte insulin action. At a tissue-specific level, this manifested as improved insulin-mediated 2-deoxyglucose uptake and suppression of lipolysis. On a whole-body level, the result was improved glucose tolerance after an intraperitoneal glucose load and increased insulin-stimulated whole-body glucose disposal during a hyperinsulinemic-euglycemic clamp. In conclusion, Foxo1 ASO therapy improved both hepatic insulin and peripheral insulin action. Foxo1 is a potential therapeutic target for improving insulin resistance.
Objective: To study the consists of polysaccharide from Ganoderma lucidum spore, its relative molecular weight (MW), and the distribution of the relative MW, then to compare the broken cellular wall spore with unbroken one in their physical and chemical properties. Methods: The polysaccharides were extracted by different methods, the monosaccharide compositions in the polysaccharide from G. lucidum were determined by HPLC and GC-MS; the relative MW and its distribution of the polysaccharide were examined by gel permeation chromatography (GPC). Results: The amount of the polysaccharide of broken spore is 1.7 times of unbroken one; both polysaccharide of broken and unbroken spore consist of rhamnose, alabinose, mannose, glucose, and galactose, there is a little difference in their relative contents; the polysaccharide of unbroken spore has only one GPC peak, its MW was 7.80 × 10 4, and the broken one has two GPC peaks, their MW were 7.8 × 10 4, and 1.17 × 10 4, respectively. Conclusion: There are same composition and different MW between the broken and unbroken spore polysaccharides. The broken spore polysaccharide has smaller MW than that of the unbroken one, it can be used to explain why the broken spore has better curative effect than the unbroken one.
We previously showed that angiotensin II (ang II) infusion in the rat produces cachexia and decreases circulating insulin-like growth factor I (IGF-I). The weight loss derives from an anorexigenic response and a catabolic effect of ang II. In these experiments we assessed potential catabolic mechanisms and the involvement of the IGF-I system in these responses to ang II. Ang II infusion caused a significant decrease in body weight compared with that of pair-fed control rats. Kidney and left ventricular weights were significantly increased by ang II, whereas fat tissue was unchanged. Skeletal muscle mass was significantly decreased in the ang II-infused rats, and a reduction in lean muscle mass was a major reason for their overall loss of body weight. In skeletal muscles, ang II did not significantly decrease protein synthesis, but overall protein breakdown was accelerated; inhibiting lysosomal and calcium-activated proteases did not reduce the ang II-induced increase in muscle proteolysis. Circulating IGF-I levels were 33% lower in ang II rats vs. control rats, and this difference was reflected in lower IGF-I messenger RNA levels in the liver. Moreover, IGF-I, IGF-binding protein-3, and IGF-binding protein-5 messenger RNAs in the gastrocnemius were significantly reduced. To investigate whether the reduced circulating IGF-I accounts for the loss in muscle mass, we increased circulating IGF-I by coinfusing ang II and IGF-I, but this did not prevent muscle loss. Our data suggest that ang II causes a loss in skeletal muscle mass by enhancing protein degradation probably via its inhibitory effect on the autocrine IGF-I system.
Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia of diabetic C57BL/KsJ-db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA as well as troglitazone suppresses the elevated hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and fructose-1, 6-bisphosphatase (FBPase) activities in C57BL/KsJ-db/db mice. In the present study, we evaluated the changes in mRNA of G6Pase and FBPase in db/db mice. Despite hyperinsulinemia, the G6Pase mRNA level of db/db mice was elevated as compared to their heterozygote littermate db/+m mice. In contrast, the FBPase mRNA level was not elevated in db/db mice. Administration of DHEA for two weeks significantly decreased the blood glucose level and the elevated G6Pase mRNA level in db/db mice. No significant changes were seen in the FBPase mRNA level after the administration of DHEA. Administration of troglitazone also decreased the blood glucose and G6Pase mRNA level in db/db mice although no changes were seen in the FBPase mRNA level. These results suggest that the elevation of G6Pase mRNA is important in elucidating the cause of insulin resistance, and that the G6Pase gene is at least one target for the hypoglycemic effects of DHEA as an insulin sensitizing agent in db/db mice.
Two hypoglycemic principles, ganoderans B and C, isolated from the fruit bodies of Ganoderma lucidum were shown to be peptidoglycans with M,s of 7400 and 5800, respectively. Physico-chemical and chemical studies demonstrated that the backbone and side chains of ganoderan B contain D-glucopyranosyl β-1 → 3 and β-1 → 6 linkages while those of ganoderan C contain D-glucopyranosyl β-1 → 3 and β-1 → 6 linkages and a D-galactopyranosyl α-1 → 6 linkage.
Simple sugars, oligosaccharides, polysaccharides, and their derivatives, including the methyl ethers with free or potentially free reducing groups, give an orange-yellow color when treated with phenol and concentrated sulfuric acid. The reaction is sensitive and the color is stable. By use of this phenol-sulfuric acid reaction, a method has been developed to determine submicro amounts of sugars and related substances. In conjunction with paper partition chromatography the method is useful for the determination of the composition of polysaccharides and their methyl derivatives.
We estimated the number of people worldwide with diabetes for the years 2010 and 2030.
Studies from 91 countries were used to calculate age- and sex-specific diabetes prevalences, which were applied to national population estimates, to determine national diabetes prevalences for all 216 countries for 2010 and 2030. Studies were identified using Medline, and contact with all national and regional International Diabetes Federation offices. Studies were included if diabetes prevalence was assessed using a population-based methodology, and was based on World Health Organization or American Diabetes Association diagnostic criteria for at least three separate age-groups within the 20-79 year range. Self-report or registry data were used if blood glucose assessment was not available.
The world prevalence of diabetes among adults (aged 20-79 years) will be 6.4%, affecting 285 million adults, in 2010, and will increase to 7.7%, and 439 million adults by 2030. Between 2010 and 2030, there will be a 69% increase in numbers of adults with diabetes in developing countries and a 20% increase in developed countries.
These predictions, based on a larger number of studies than previous estimates, indicate a growing burden of diabetes, particularly in developing countries.
Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) are important in control of blood glucose homeostasis, and are considered to be potential targets for antidiabetic drugs. Astragaloside IV has been reported to have a hypoglycemic effect. However, the biochemical mechanisms by which astragaloside IV regulates hepatic glucose-metabolizing enzymes remain unknown. The present study examines whether GP and G6Pase mediate the hypoglycemic effect of astragaloside IV.
Type 2 diabetic mice were treated with astragaloside IV for 2 weeks. Blood glucose and insulin levels were measured by a glucometer and the ELISA method, respectively. Total cholesterol (TC) and triglyceride (TG) levels were determined using Labassay kits. Activities of hepatic GP and G6Pase were measured by the glucose-6-phosphate dehydrogenase-coupled reaction. The mRNA and protein levels of both enzymes were determined by real-time RT-PCR and Western blotting.
Astragaloside IV at 25 and 50 mg/kg significally decreased the blood glucose, TG and insulin levels, and inhibited the mRNA and protein expression as well as enzyme activity of GP and G6Pase in diabetic mice.
Astragaloside IV exhibited a hypoglycemic effect in diabetic mice. The hypoglycemic effect of this compound may be explained, in part, by its inhibition of hepatic GP and G6Pase activities.
Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) play an important role in the control of blood glucose homeostasis and are proposed to be potential targets for anti-diabetic drugs. Geniposide is an iridoid glucoside extracted from Gardenia jasminoides Ellis fruits and has been reported to have a hypoglycemic effect. However, little is known about the biochemical mechanisms by which geniposide regulates hepatic glucose-metabolizing enzymes. The present study investigates whether the hypoglycemic effect of geniposide is mediated by GP or G6Pase.
Type 2 diabetic mice, induced by a high-fat diet and streptozotocin injection, were treated with or without geniposide for 2 weeks. Blood glucose levels were monitored by a glucometer. Insulin concentrations were analyzed by the ELISA method. Total cholesterol (TC) and triglyceride (TG) levels were measured using Labassay kits. Activities of hepatic GP and G6Pase were measured by glucose-6-phosphate dehydrogenase-coupled reaction. Real-time RT-PCR and Western blotting were used to determine the mRNA and protein levels of both enzymes.
Geniposide (200 and 400 mg/kg) significantly decreased the blood glucose, insulin and TG levels in diabetic mice in a dose-dependent manner. This compound also decreased the expression of GP and G6Pase at mRNA and immunoreactive protein levels, as well as enzyme activity.
Geniposide is an effective hypoglycemic agent in diabetic mice. The hypoglycemic effect of this compound may be mediated, at least in part, by inhibiting the GP and G6Pase activities.
In this study, we evaluated the pharmacological effects of Ganoderma lucidum (G. lucidum) (water-extract) (0.003, 0.03 and 0.3g/kg, 4-week oral gavage) consumption using the lean (+db/+m) and the obese/diabetic (+db/+db) mice. Different physiological parameters (plasma glucose and insulin levels, lipoproteins-cholesterol levels, phosphoenolpyruvate carboxykinase (PEPCK), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) and isolated aorta relaxation of both species were measured and compared. G. lucidum (0.03 and 0.3g/kg) lowered the serum glucose level in +db/+db mice after the first week of treatment whereas a reduction was observed in +db/+m mice only fed with 0.3g/kg of G. lucidum at the fourth week. A higher hepatic PEPCK gene expression was found in +db/+db mice. G. lucidum (0.03 and 0.3g/kg) markedly reduced the PEPCK expression in +db/+db mice whereas the expression of PEPCK was attenuated in +db/+m mice (0.3g/kg G. lucidum). HMG CoA reductase protein expression (in both hepatic and extra-hepatic organs) and the serum insulin level were not altered by G. lucidum. These data demonstrate that G. lucidum consumption can provide beneficial effects in treating type 2 diabetes mellitus (T2DM) by lowering the serum glucose levels through the suppression of the hepatic PEPCK gene expression.
The Spontaneously Diabetic Torii (SDT) rat has recently been established as a new model of non-obese type 2 diabetes. In this study, we examined changes in hepatic glucose metabolism in prediabetic and diabetic SDT rats compared with age-matched control rats. The prediabetic state was confirmed at 16 weeks of age, and the diabetic state was confirmed at 24 and 32 weeks of age. Decreases in glucokinase mRNA levels and activity were observed in the prediabetic state. In this state, glycogen synthase activity and glycogen content were also decreased in the SDT rat. In addition to the above changes, glycogen phosphorylase mRNA and activity were decreased and gluconeogenetic enzyme mRNA levels were significantly increased in the diabetic state. These results indicate there is a great potential that abnormalities in hepatic glucose metabolism play a role in the progression to onset of diabetes. We suggest that the SDT rat is a valuable diabetic model for investigations into mechanisms or causes of progression to diabetes.
Transcription of the gene for phosphoenolpyruvate carboxykinase is regulated by several hormones which control the level of glucose synthesis in vertebrate animals. A 490 bp segment located at the 5' end of the structural gene contains the necessary regulatory elements to account for the pattern of transcriptional regulation characteristic of the phosphoenolpyruvate carboxykinase gene. Multiple cis binding sites within the promoter and nuclear binding proteins have been identified and shown to play a role in the regulation of gene transcription. The interaction of these transcription factors with each other and with the phosphoenolpyruvate carboxykinase promoter is central to the regulated expression of this gene. The key role of cAMP and insulin in controlling the level of gene transcription will be discussed and related to the function of transcription factors currently known to regulate the tissue specific expression of the phosphoenolpyruvate carboxykinase gene.
Ganoderan B increased the plasma insulin level in normal and glucose-loaded mice but elicited no effect on insulin binding to isolated adipocytes. Administration of ganoderan B elicited significant increases of the activities of hepatic glucokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase, decreased the hepatic glucose-6-phosphate and glycogen synthetase activities and did not affect the activities of hexokinase and glycogen phosphorylase. Ganoderan B reduced the glycogen content in the liver but had no influence on total cholesterol and triglyceride levels in the plasma and liver.
This paper describes a laboratory trial of a glucose analyser (Beckman Instruments Ltd.), an instrument specifically designed to measure serum or plasma glucose.
Glucose-6-phosphatase catalyzes the final step of glucose production by liver and kidney. Though its strategic position has sparked interest in its regulation, difficulty with isolating a pure, stable enzyme has slowed progress. Virtually all previous work examining the physiologic regulation of this enzyme has relied on estimates of glucose-6-phosphatase activity in crude microsome preparations. The recent cloning of human and murine glucose-6-phosphatase cDNAs has now allowed study of its mRNA expression. We studied the effect of acute, streptozotocin-induced diabetes on hepatic microsomal glucose-6-phosphatase activity and mRNA expression in young (89 +/- 3 g), juvenile (304 +/- 4 g) and adult (512 +/- 10 g) rats. In control rats, mRNA expression and enzyme activity was similar among the three age groups. Streptozotocin-induced diabetes significantly increased the enzyme activities in both intact and triton-treated microsomes in all groups of rats (p < 0.001). Glucose-6-phosphatase mRNA expression was increased in the diabetic rats as well (p < 0.0001). Blood glucose concentrations correlated significantly with glucose-6-phosphatase mRNA level (p < 0.005) and both intact (p < 0.002) and triton-treated (p < 0.001) microsomal glucose-6-phosphatase activity. Both intact and triton-treated microsomal glucose-6-phosphatase activity correlated with mRNA level (p < 0.001, for each). We conclude that acute streptozotocin-diabetes increase expression of glucose-6-phosphatase mRNA and this contributes to the increased glucose-6-phosphatase activity seen with diabetes mellitus.
Glucuronoxylomannan (AC) from the fruiting bodies of Tremella fuciformis exhibited a significant dose-dependent hypoglycemic activity in normal mice and also showed a significant activity in streptozotocin-induced diabetic mice, by intraperitoneal (i.p.) administration. The activities of AC-derivatives such as a product of AC which side chains had been removed were lower than that of native AC. AC raised the plasma insulin level in normal mice. Administration of AC to normal mice significantly increased the activities of hepatic hexokinase and glucose-6-phosphatase dehydrogenase, but it decreased that of hepatic glucose-6-phosphatase. Furthermore, AC reduced the glycogen content in the liver, increased the total lipid in epididymal adipose tissue, and lowered the plasma cholesterol level. The foregoing results indicated that the hypoglycemic activity of AC in normal mice was at least responsible for the increase of insulin secretion and for the acceleration of glucose metabolism. Single oral administration at a dose of 50-300 mg/kg of AC did not affect the plasma glucose level in normal mice, but continuous oral administrations of the AC solution (0.75 g/l) instead of water for a long time was found to be effective on the plasma glucose level in both experiments of the mice injected once i.p. with streptozotocin (170 mg/kg) at 0 d of AC administration and streptozotocin-induced diabetic mice.
Crude polysaccharides were obtained from a hot-water extract and alkaline extracts of the cultural mycelium of Cordyceps sinensis. They showed significant activity in normal mice and streptozotocin-induced diabetic mice as a result of intraperitoneal (i.p.) injection. A crude polysaccharide (CS-OHEP) obtained from 5% sodium hydroxide extract slightly lowered the plasma glucose level in normal mice by oral (p.o.) administration. A neutral polysaccharide (CS-F30) exhibited higher hypoglycemic activity than its crude polysaccharide (CS-OHEP), exhibited by i.p. injection, and it significantly lowered the glucose level by p.o. administration (50 mg/kg). However, it hardly affected the plasma insulin level in normal mice. CS-F30 ([alpha]D + 21 degrees in water) is composed of galactose, glucose and mannose (molar percent, 62:28:10), and its molecular weight is about 45000.
A glucan (AG-HN1, [alpha]D +24 degrees) and a heteroglycan (AG-HN2, [alpha]D +26 degrees) were isolated from a hot-water extract of the fruiting bodies of Agrocybe cylindracea. The structures were investigated by a combination of chemical and spectroscopic methods. The results indicated that high molecular weight glucan AG-HN1 is primarily a beta-(1-->6)-branched (1-->3)-beta-D-glucan containing small amounts of (1-->4)-linked and (1-->6)-linked glucopyranosyl residues. Low molecular weight heteroglycan AG-HN2 gives galactose, glucose, fucose, and mannose on hydrolysis and appears to be chiefly composed of (1-->6)-linked gluco- and galacto-pyranosyl residues, many of them branched, and various nonreducing terminal residues. AG-HN1 showed a remarkable hypoglycemic activity in both normal and streptozotocin-induced diabetic mice by ip administration, and its activity was higher than that of AG-HN2.
Expression of key regulatory enzymes involved in glucose metabolism was studied in the livers of Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin dependent diabetes mellitus. The activity and mRNA levels of glucokinase and L-type pyruvate kinase was increased in the liver of OLETF rats compared with control rats. There was no such remarkable change in liver-type phosphofructokinase. The activities of glucose-6-phosphatase and fructose-1,6-biphosphatase also increase despite high plasma levels of glucose and insulin. The activity of phosphoenolpyruvate carboxykinase did not show any significant change. The mRNA levels for fructose-1,6-biphosphatase, and phosphoenolpyruvate carboxykinase exhibited no marked changes. These results suggest that the expression of glucose-6-phosphatase and fructose-1,6-biphosphatase is disordered in OLETF rats.
An acidic polysaccharide (TAP) was isolated from a hot-water extract of the fruiting bodies of Tremella aurantia. It showed remarkable hypoglycemic activity in normal mice and two diabetic mouse models, streptozotocin-induced diabetes and genetic diabetes, following intraperitoneal administration. Continuous oral administration of TAP solution (0.5g/l) for a long period was found to be also effective in hyperglycemia in glucose-loaded mice and no harmful physical effects were found. TAP had an [alpha]D -7 degrees in water, and its molecular weight was estimated to be about 1500000. TAP is composed of mannose, xylose, glucuronic acid and glucose (molar ratio, 4:2:1:0.3), and it contains 2.2% of O-acetyl groups.
A polysaccharide (CS-F30) obtained from the cultural mycelium of Cordyceps sinensis showed potent hypoglycemic activity in genetic diabetic mice after intraperitoneal administration, and the plasma glucose level was quickly reduced in normal and streptozotocin-induced diabetic mice after intravenous administration. Administration of CS-F-30 to normal mice significantly increased the activities of hepatic glucokinase, hexokinase and glucose-6-phosphate dehydrogenase, although the glycogen content in the liver was reduced. Furthermore, CS-F30 lowered the plasma triglyceride level and cholesterol level in mice.
The mRNA level of the catalytic subunit of rat liver glucose-6-phosphatase (Glu-6-Pase) was regulated by hormones commensurate with activity changes in vivo. Insulin exerts a dominant negative effect on the mRNA levels of Glu-6-Pase. Both mRNA levels and activities of the enzyme are low in the fed and refed state where insulin levels are elevated. Insulin administration to diabetic rats also decreases levels of mRNA and Glu-6-Pase activity. Insulin at a concentration of 1 nmol/l completely overcomes the stimulatory effect of glucocorticoids on Glu-6-Pase message levels in FAO hepatoma cells. The stimulatory response to glucocorticoid in FAO cells is biphasic, with maxima seen at 3 and 18 h after hormone addition (respectively 1.6- and 3.3-fold). 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) causes a fourfold increase in Glu-6-Pase mRNA at 3 h in FAO cells. The gene of rat liver Glu-6-Pase is 13 kilobases in length and comprised of 5 exons. The exon-intron structure is completely conserved when compared with the mouse and human genes. A 0.5-kb 3'-untranslated region, which is present in rat and mouse liver Glu-6-Pase cDNA, is absent in the Glu-6-Pase gene reported here, indicating the possible duplication of either the terminal fifth exon or the entire gene. The promoter region contains a consensus core CCAAT element at position -207 and a TATAAA at position -31. Several possible response elements have been identified in the 5'-flanking region (from a HindIII site at position -1641). A consensus glucocorticoid response element is located at base pair -1552, a 9/10 match of the insulin response sequence is located at position -1449, and a 7/8 match of the cAMP response element is located at position -164.
Phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) is a key enzyme in the synthesis of glucose in the liver and kidney and of glyceride-glycerol in white adipose tissue and the small intestine. The gene for the cytosolic form of PEPCK (PEPCK-C) is acutely regulated by a variety of dietary and hormonal signals, which result in alteration of synthesis of the enzyme. Major factors that increase PEPCK-C gene expression include cyclic AMP, glucocorticoids, and thyroid hormone, whereas insulin inhibits this process. PEPCK-C is absent in fetal liver but appears at birth, concomitant with the capacity for gluconeogenesis. Regulatory elements that control transcription of the PEPCK-C gene in liver, kidney, and adipose tissue have been delineated, and many of the transcription factors that bind to these elements have been identified. Transgenic mice have been especially useful in elucidating the physiological roles of specific sequence elements in the PEPCK-C gene promoter and in demonstrating the key role played at these sites by the isoforms of CAAT/enhancer binding protein in patterning of PEPCK-C gene expression during the perinatal period. The PEPCK-C gene provides a model for the metabolic control of gene transcription.
The hypoglycemic effect of water-soluble polysaccharide(FA) from fruiting bodies of Auricularia auricula-judae Quel. was investigated on genetically diabetic mice (KK-Ay) from 10 to 14 weeks of age. Male mice were divided into 3 groups, the control group and FA-fed group having free access to the control diet or FA diet (30 g of FA/kg of diet). The food-restricted group had restricted access to the control diet at the level of the diet consumed by the FA-fed group. Compared with the control group, FA supplementation had a significant effect in lowering plasma glucose, insulin, urinary glucose, and food intake. FA administration also increased the tolerance to intraperitoneal glucose loading and the hepatic glycogen content. In the food-restricted group, the reduced food intake slightly lowered the plasma and urinary glucose levels, but did not improve hyperinsulinemia and glucose tolerance. This study shows that FA had a hypoglycemic effect on KK-Ay mice, and the reduced food consumption was not a major factor which contributed to the hypoglycemic action of FA.
We investigated the ameliorating effects of the three groups of water-soluble polysaccharides, a mixture of crude polysaccharides (FA), acidic polysaccharide fractions (FA-A), and neutral polysaccharide fractions (FA-N), obtained from the hot water extracts of the fruit bodies of Auricularia auricula-judae Quel. In genetically diabetic KK-Ay mice from 6 to 11 weeks of age. Male mice were divided into five dietary groups: 1) control group, given a basal diet; 2) FA group, given an FA diet (15 g FA/kg diet); 3) FA-A group, given an FA-A diet (8 g FA-A/kg diet); 4) low FA-N group, given a low FA-N diet (2 g FA-N/kg diet); and 5) high FA-N group, given a high FA-N diet (8 g FA-N/kg diet). Compared with the control diet, FA supplementation had significant effects in lowering fasting and nonfasting blood glucose, HbA1c, urinary glucose, food intake, and water intake. FA administration also improved glucose tolerance to intraperitoneal glucose loading, but it did not affect the nonfasting insulin level. FA-N supplementation had dose-dependent effects in lowering fasting and nonfasting food glucose, insulin, HbA1c, urinary glucose, food intake, and water intake. However, the glucose tolerance was not ameliorated by either the low or the high FA-N diet. FA-A administration showed no beneficial effects in KK-Ay mice.
A polysaccharide (CS-F10) purified from a hot water extract of the cultured mycelium of Cordyceps sinensis was composed of galactose, glucose and mannose in a molar ratio of 43:33:24; its molecular weight was estimated to be about 15000. The results of chemical and spectroscopic investigations suggest that CS-F10 has a comb-type structure, and has alpha-D-glucopyranosyl residues on the terminal of the side-chains and characteristic sugar residues of C. sinensis i.e., 1,5-linked beta-D-galactofuranosyl residues. CS-F10 significantly lowered the plasma glucose level in normal, streptozotocin (STZ)-induced diabetic and epinephrine-induced hyperglycemic mice after intraperitoneal administration (50 mg/kg). Administration of CS-F10 to STZ-induced diabetic mice significantly increased the activity of hepatic glucokinase. A significant reduction in the hepatic glucose output was observed following the infusion of CS-F10 using the perfused rat liver. CS-F10 also significantly decreased protein content of facilitative glucose transporter isoform 2 (GLUT2) from rat liver following i.p. administration. These effects presumably contribute to the hypoglycemic activity.