Views: 4 Author: 菌物健康 Publish Time: 2022-08-30 Origin: 魏奇，翁馨，吴艳钦，等.食用菌多糖降血糖活性及其作用机制的研究进展[J].食品工业.2022，43（7）：250~254.
Diabetes is a metabolic disease characterized by hyperglycemia. With the improvement of living standards, people's lifestyle and dietary structure have also changed. In recent years, diabetes has seriously endangered human health. Diabetes has become one of the three major fatal diseases of human beings with high prevalence and low treatment rate, and its mortality rate is second only to cardiovascular and cerebrovascular diseases and cancer. Type 1 diabetes and type 2 diabetes are the 2 main categories of diabetes. Type 1 diabetes refers to the fact that the body cannot produce insulin normally, and oral hypoglycemic drugs alone cannot lower blood sugar, and the patient needs to take insulin for treatment. Type 2 diabetes is also often referred to as non-insulin-dependent diabetes. Lack of exercise, obesity, being overweight, unhealthy diet and psychosocial stress all increase the risk of developing type 2 diabetes. If the body maintains a high blood sugar state for a long time, it will cause a variety of diabetic complications and harm human health [1] .
Studies have shown that edible fungus polysaccharides can lower blood lipids, lower blood sugar, protect liver and gallbladder, and enhance human immunity . Polysaccharide is the main bioactive substance of edible fungi and meets the requirements of the World Health Organization as an immune enhancer. Its greatest advantages are low toxicity and few side effects. Therefore, the development of medicines and health products of edible fungus polysaccharides has become one of the hot research fields of edible fungus deep processing.
Diabetes is mainly treated by insulin injection, oral hypoglycemic drugs and diet therapy. Biguanides, sulfonylureas, thiazolidinediones, etc. are widely used in clinical treatment of diabetes, such as metformin, glyburide, glimepiride, gliclazide, rosiglitazone and pioglitazone, etc. drug. However, long-term use of these drugs will cause inevitable toxic and side effects to the human body, which may easily lead to adverse reactions such as hypoglycemia, vomiting and diarrhea, thus limiting their application. Therefore, it is of great significance to find drugs with no side effects and better hypoglycemic effect. Exploring the hypoglycemic activity of edible fungus polysaccharide and its mechanism of action can provide a scientific reference for the research and development of edible fungus polysaccharide hypoglycemic drugs.
1. The effect of edible fungus polysaccharide on the activity of digestive enzymes
Amylase, cellulase, α-glucosidase and maltase are common digestive enzymes in the human intestinal tract. The main target of these digestive enzymes is the α-1,4 glycosidic bond of carbohydrates, which can hydrolyze carbohydrates and other substances into glucose. Therefore, these digestive enzymes play a very important role in the process of digestion and absorption. The main reason for the increase of postprandial blood glucose level is the increase of glucose level in the blood. If the body is in a state of high blood sugar for a long time, it will lead to a decrease in the body’s insulin sensitivity or insulin resistance, thereby inducing diabetes and its complications [ 3] . α-Glucosidase is an important class of enzymes in the sugar metabolism pathway, its main action site is the glucosidic bond, which can hydrolyze sugars and take glucose as the final product. Therefore, α-glucosidase becomes an important therapeutic target for regulating postprandial blood glucose. By inhibiting the activity of α-glucosidase, the rate of decomposition of carbohydrates into glucose can be effectively slowed down, thereby reducing postprandial blood glucose levels and preventing diabetes. Edible fungus polysaccharide can be used as an α-glucosidase inhibitor, which has the effect of controlling postprandial blood sugar rise, and has the effect of high safety and low intestinal side effects. Edible fungus polysaccharide has a good inhibitory effect on these digestive enzymes, and can reduce the rate of carbohydrate decomposition into glucose, thereby effectively avoiding the rapid rise of postprandial blood sugar level, thus exerting its hypoglycemic effect. Table 1 summarizes the activity of some edible fungus polysaccharides in regulating digestive enzymes.
It can be seen from Table 1 that the black fungus polysaccharide has an inhibitory effect on α-glucosidase. In vivo animal experiments found that the body weight, hexokinase and succinate dehydrogenase activities of diabetic mice treated with black fungus polysaccharide were increased, which indicated that black fungus polysaccharide had a hypoglycemic effect [4] . Li Shunfeng et al. [5] found that acetylated lentinus polysaccharide could improve its inhibitory effect on α-glucosidase, and the concentration of lentinus polysaccharide was positively correlated with the inhibitory effect of α-glucosidase. From this, it can be seen that the acetylated lentinan has a dose-dependent inhibitory effect on α-glucosidase. Dong Wenxia [6] found that Inonotus obliquus polysaccharides (NIOP1-S and HIOP1-S) showed strong α-glucosidase inhibitory activities (IC50 were 24.22 and 29.95 μg/mL, respectively), while the positive control aka The IC50 of boose is 1020 μg/mL. HIOP1-S is a competitive inhibition of α-glucosidase, and NIOP1-S is a non-competitive inhibition of α-glucosidase.
In addition to α-glucosidase, edible fungus polysaccharide can also exert its hypoglycemic effect by inhibiting the activity of amylase and delaying the rate of hydrolysis of carbohydrates into glucose. Luo Jiayuan et al [7] found that black fungus polysaccharide can effectively inhibit the activity of α-amylase, and improve the delay index of glucose dialysis, so as to achieve the purpose of lowering blood sugar. Zhang Bohua et al [8] found that the compound polysaccharides of Flammulina velutipes , Mushrooms and Lentinus edodes can effectively inhibit the activity of α-amylase. The inhibitory activity of the compound edible fungus polysaccharide of Flammulina velutipes, Mushroom globulus and Lentinus edodes on α-amylase was greater than that of single variety polysaccharide edible fungus polysaccharide. Zhang Chen [9] research proved that the mycelial polysaccharides PMPS-1 and PMPS-2 of Pleurotus eryngii obtained by water extraction and alcohol precipitation showed strong inhibitory activities of α-amylase and α-glucosidase. Among them, PMPS-2 has a stronger inhibitory effect on α-glucosidase and α-amylase than PMPS-1. In vivo experiments also proved that Pleurotus eryngii polysaccharide can reduce the blood sugar level in diabetic mice and improve lipids in diabetic mice. Metabolic disorders have a positive effect on the prevention and treatment of diabetes. It can be seen that edible fungus polysaccharides can reduce blood sugar by regulating the activity of digestive enzymes.
2. The effect of edible fungus polysaccharide on improving insulin resistance
Insulin is a protein hormone secreted by pancreatic β-cells and is the only hormone in the body that lowers blood sugar. Diabetic patients are prone to the occurrence of insulin resistance, resulting in abnormal recognition of insulin receptors, resulting in a decline in the body's uptake and utilization of glucose, making the body prone to metabolic syndrome. Studies have confirmed that edible fungus polysaccharides can promote the secretion of insulin, improve insulin sensitivity and repair damaged islet cells.
Chen et al [10] obtained Grifola frondosa polysaccharides with hypoglycemic activity from Grifola frondosa fruiting bodies. Grifola frondosa polysaccharide can repair the damaged islet cells in streptozotocin (STZ)-induced diabetic mice, and can alleviate the insulin resistance of diabetic mice, thereby reducing blood sugar levels. Grifola frondosa polysaccharide can increase the protein level of insulin receptors in the liver, promote the body's absorption of glucose, improve the effect of insulin resistance, and thus repair the insulin signaling pathway.
Kim et al. [11] showed that Agaricus blazei polysaccharides have hypoglycemic activity, can repair the damaged pancreatic tissue in diabetic mice, promote the proliferation of islet cells, and stimulate islet cells to secrete insulin. The research of Gong Haiquan [12] showed that Armillaria polysaccharides can improve insulin sensitivity in diabetic mice and have a repairing effect on damaged islet cells in diabetic mice. Ganoderma lucidum polysaccharide can increase the secretion of insulin, increase the concentration of insulin in plasma, and increase the activity of enzymes related to glucose metabolism in the liver to promote the absorption of glucose by the liver, thereby achieving the effect of stabilizing blood sugar [13] . Yu Yudie et al. [14] found that polysaccharides from the fruiting bodies of Inonotus obliquus could improve the glucose consumption capacity of HepG2 cells, accelerate the metabolism of glucose by cells, and thus enhance the sensitivity of liver cells to insulin.
3. Polysaccharide regulation of edible fungi and expression of glucose metabolism-related factors
from Ganoderma lucidum, which can effectively reduce the expression of glucose-6-phosphate (G6Pase) and glycogen phosporylase (GP) mRNA in the liver of diabetic mice. It inhibits the decomposition of liver glycogen and the occurrence of gluconeogenesis, thereby reducing the fasting blood glucose level of diabetic mice. Ganoderma lucidum polysaccharide can effectively reduce the blood glucose level and body weight of ob/ob mice. Its mechanism of action is to activate the PI3K/Akt pathway, up-regulate the expression of AMPK and glucose transporter 4 (GLUT4), and promote the transport of GLUT4 to the plasma membrane. , and then inhibit the expression of protein tyrosine phosphatase 1B and IRS1 in the insulin signal transduction pathway, so as to achieve the purpose of improving insulin resistance and lowering blood sugar level [15] .
Tremella polysaccharide can regulate glucose metabolism, inhibit G6Pase, activate liver hexokinase, glucokinase and glucose-6-phosphate dehydrogenase, and accelerate the occurrence of glucose metabolism while increasing the body's insulin level [16] . Grifola frondosa polysaccharide can up-regulate the mRNA expression of insulin receptor substrate 1 (IRS1) and phosphatidylinositide-3-Kinase (PI3K), when the cell surface insulin receptor binds to IRS Then, IRS is phosphorylated, and the phosphorylated IRS can activate PI3K and downregulate the expression of c-jun N-terminal kinase 1/2 (JNK1/2) mRNA, thereby activating PI3K. PI3K/Akt pathway promotes the synthesis of glycogen and lowers blood sugar, thereby reducing insulin resistance in the body [17] .
A large number of studies have found that edible and medicinal bacterial polysaccharides can regulate its key proteins, key genes and key signaling pathways through signal pathways such as glucose metabolism, insulin resistance, oxidative stress and inflammation, and exert its hypoglycemic effect. However, the causes of glucose metabolism disorders in diabetic patients are often not just mutations in several genes or abnormal target functions, but usually involve abnormal changes at the overall level. Therefore, more scientific research is needed for further research. Explore and corroborate.
4. Edible fungus polysaccharides reduce oxidative stress
Due to the long-term hyperglycemia of the body, diabetic patients will induce the continuous accumulation of reactive oxygen radicals in the body, resulting in oxidative stress and other occurrences in the body, which will damage biological macromolecules such as lipids, proteins and nucleic acids in the body. Oxidative stress impairs the body's energy efficiency at various levels, thereby exacerbating diabetes and its complications, such as diabetic retinopathy, vascular disease, and diabetic neuropathy.
Liu Hui [18] found that the fruiting body polysaccharides of Pleurotus eryngii can increase the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione peroxidase (GSH-Px) in pancreatic tissue of diabetic mice. Catalase (CAT) activity decreased the content of malondialdehyde (MDA), which indicated that the fruiting body polysaccharide of Pleurotus eryngii could protect pancreatic tissue and resist oxidative damage. In vivo studies have found that the fruiting body polysaccharide of Pleurotus eryngii can also improve the glucose metabolism disorder in streptozotocin-induced diabetic mice, reduce oxidative stress damage, and inhibit the occurrence of diabetes and its complications.
Zhao et al. [19] found that Cordyceps militaris acid polysaccharide can reduce the blood glucose level in type 2 diabetic mice by reducing the accumulation of lipids in serum and the effect of lipid peroxidation, enhancing the activity of antioxidant enzymes. Zhang et al. [20] found that Hericium erinaceus polysaccharide could reduce the oxidative damage and inflammation to the liver, kidney and pancreas by increasing the activity of antioxidant enzymes in diabetic mice and reducing the content of MDA. Zhang Lan [21] found that the polysaccharide of Boletus aureus has strong antioxidant activity and can be used as a natural antioxidant. In vivo experiments also confirmed that the polysaccharide of Boletus aureus has anti-diabetic effect, and its hypoglycemic effect mainly depends on Antioxidative activity of the polysaccharides from Boletus aureus. Lin Lin [22] found that Flammulina velutipes mushroom polysaccharide and Pleurotus eryngii polysaccharide can increase the activities of SOD, CAT and GSH-Px in the kidneys of diabetic mice, and reduce the content of MDA in the kidneys. The antioxidant capacity of Pleurotus eryngii polysaccharide and Flammulina velutipes polysaccharide increased with the increase of their concentration.
Black fungus polysaccharide can enhance the activity of antioxidant enzymes in diabetic mice, reduce lipid peroxidation, inhibit oxidative stress, and reduce blood lipids, thereby reducing blood sugar levels in diabetic mice [23] . Zhou Lingyun et al. [24] obtained TOPS-1 from Trametes orientalis polysaccharide showed hypoglycemic effect. Tramioporus orientalis polysaccharide can promote the uptake of glucose by adipocytes. Animal experiments show that TOPS-1 can significantly reduce the fasting blood glucose level of streptozotocin-induced diabetic mice. Its hypoglycemic effect may be related to reducing the level of oxidative stress and reducing the Disorders of fat metabolism in patients with diabetes mellitus.
5. The role of edible fungus polysaccharides in regulating intestinal flora
The gut microbiota plays an important role in digesting carbohydrates and maintaining energy balance. The occurrence of common diseases such as obesity, gout and diabetes is closely related to the imbalance of intestinal flora. A large number of studies have found that edible mushroom polysaccharides can regulate the dynamic balance of intestinal flora, thereby playing a role in the treatment of diabetes. Therefore, it is expected to provide a new theoretical basis for the prevention and treatment of diabetes by combining dietary changes with natural drug treatment without toxic side effects. Luo You [25] found that high-sugar and high-fat diets can increase the permeability of the intestinal tract of diabetic mice, which will have a certain impact on the diversity and structural stability of the intestinal flora.
Cordyceps militaris polysaccharide can reduce the permeability of intestinal epithelial cells in diabetic mice, slow down the absorption of sugar in the gastrointestinal tract, and improve insulin sensitivity by regulating amino acid metabolism, energy metabolism of the body and intestinal flora, so as to reduce blood sugar. effect.
The breakdown of carbohydrates by gut bacteria produces short-chain fatty acids such as acetate, propionate, butyrate, and lactate. Among them, acetic acid helps keep the intestinal environment stable, and butyric acid can increase the content of Lactobacillus in the intestinal tract and reduce the content of E. coli, thereby maintaining intestinal health. Therefore, the study of short-chain fatty acids plays an important role in exploring the regulation of intestinal flora by edible fungus polysaccharides.
The study found that Grifola frondosa polysaccharides can reduce the ratio of Firmicutes and Bacteroidetes to regulate the composition of the intestinal flora of rats, thereby increasing the total short-chain fatty acids, acetate, and propionate in the intestine of rats with non-alcoholic fatty liver disease. Acid, butyric and valeric acid content. Grifola frondosa polysaccharides can promote the synthesis and excretion of bile acids in the liver, thereby inhibiting hyperlipidemia caused by a high-fat diet [26] . Zhang Ruifang [27] established a high-fat and high-sugar biological model of mice by feeding high-fat and high-sugar. The study found that Ganoderma lucidum polysaccharide F31 and Grifola frondosa polysaccharide F2 could increase bile salt hydrolase-producing bacteria (Lactobacillus and Bacteroides) and The abundance of polysaccharide-utilizing bacteria (Bacteroidetes and Rosa) regulates the metabolic pathway of bile acids and improves glucose and lipid metabolism.
Ganoderma lucidum polysaccharide can increase the content of acetic acid and propionic acid in the intestine of high-fat diet-induced diabetic rats, reduce the content of butyric acid, and regulate the intestinal bacteria of diabetic rats by increasing the beneficial bacteria in the intestinal flora and reducing the harmful bacteria The composition structure of the group can alleviate the disorder of glucose metabolism in diabetic rats [28] . It can be seen that edible mushroom polysaccharides may play a role in lowering blood sugar by regulating intestinal flora.
Sun et al. [29] found that Poria polysaccharides can change the microbial community structure in the gut of ob/ob diabetic mice, reduce the ratio of Firmicutes and Bacteroidetes, promote glucose and lipid metabolism in the body, and improve ob/ob The content of butyric acid in the intestinal tract of diabetic mice can improve the damage of intestinal mucosa and protect the integrity of intestinal mucosa. It can be seen that Poria polysaccharides can improve hyperglycemia and hyperlipidemia by regulating the microbial community structure in the gut of ob/ob mice.
Phellinus linteus polysaccharide (800 mg/kg) continuously administered to diabetic rats for 8 weeks can increase the content of short-chain fatty acid-producing bacteria in the intestinal tract of diabetic rats, and reduce the content of opportunistic pathogens, and the Phellinus linteus polysaccharide can effectively It can repair the thickness of intestinal mucosa and promote the production of short-chain fatty acids, thereby reducing intestinal permeability and improving glucose tolerance in diabetic rats [30] . In summary, edible fungus polysaccharide has the effect of regulating intestinal flora, mainly by increasing the number of beneficial bacteria in the intestine and reducing the number of harmful bacteria in the intestine, thereby maintaining the balance of intestinal flora.
6. Conclusion and Outlook
Obtaining polysaccharide substances with hypoglycemic effect from natural and safe edible fungi, and studying its regulation mechanism on the body can provide a theoretical basis for the research and development of new hypoglycemic drugs. The edible fungus polysaccharide with hypoglycemic effect has a very broad application prospect in the field of functional food and medicine. However, due to the wide variety of edible fungi and the complex composition of edible fungi polysaccharides, the current research on the hypoglycemic activity of edible fungi polysaccharides and its mechanism of action still has certain limitations. There are still many problems to be solved in the future, such as: the mechanism of action of edible fungus polysaccharide in lowering blood sugar is mostly related to some specific proteins and genes and the action sites on key metabolic pathways. The research on the overall metabolic changes that occurred is relatively limited; the structure of edible fungus polysaccharide is complex, and the hypoglycemic activity and mechanism of the single component of edible fungus polysaccharide are relatively limited; the research on the hypoglycemic activity and mechanism of edible fungus polysaccharide is mostly in At the cell and animal level, there are relatively few research reports related to clinical trials, and further clinical trial research is needed; the research on the hypoglycemic effect of edible fungus polysaccharides lacks the understanding and treatment of diabetic complications, therefore, it is necessary to conduct in-depth research on edible fungi The role of polysaccharides on diabetes complications; the development of metabolomics in food nutrition and drug development is not yet fully mature, and it is necessary to further combine proteomics and transcriptomics for multi-omics combined analysis to further elaborate scientific issues in order to fully understand The preventive and therapeutic effects of edible mushroom polysaccharides on diabetes.
