Diabetes mellitus (DM) is the third most common non-infectious disease leading to early disability and high mortality. Moreover, the number of patients is growing every year. The main symptom of DM is hyperglycemia. Increased levels of blood glucose activate polyol, hexosamine, and protein kinase metabolic pathways cause the intensification of non-enzymatic glycosylation and nitration of macromolecules. This, in turn, leads to the development of oxidative and nitrative stresses and secondary complications, such as different kinds of micro- and macroangiopathies. Metabolic disorders caused by insulin deficiency in diabetes significantly impede the functioning of a homeostasis system, which change the physical, biochemical, morphological, and functional properties of blood cells. As a result, the oxygen-transport function of red blood cells (RBCs), rheological properties of the blood, and functions of immunocompetent cells as well as the process of apoptosis are primarily affected. Modern pharmacotherapy focuses on the search for new preparations that aim to decrease blood glucose levels. Undesirable side effects and adverse reactions caused by synthetic medicines led to the search and investigation of new preparations of natural origin. Medicinal mushrooms play an important role among such new preparations. They are a source of a large number of high- and low-molecular compounds with pronounced biological effects. Our investigations show pronounced hypoglycemic and anti-anemic action of submerged cultivated mycelium powder of medicinal mushrooms Agaricus brasiliensis (A. brasiliensis) and Ganoderma lucidum (G. lucidum) on streptozotocin-induced DM in rats. Also, we showed that mycelium powders have membrane protective properties as evidenced by the redistribution of RBC populations towards the growth of full functional cell numbers. Normalization of parameters of leukocyte formula and suppression of apoptosis of white blood cells in diabetic rats treated with A. brasiliensis and G. lucidum mycelia indicates pronounced positive effects of these strains of mushrooms. Thus, the use of medicinal mushrooms for treatment of DM and in prevention development of its secondary complications might be a new effective approach of this disease’s cure. This article is aimed at summarizing and analyzing the literature data and basic achievements concerning DM type 1 treatment using medicinal mushrooms and showing the results obtained in our research.

Diabetes mellitus (DM) is accompanied by the development of hypoxia, which disturbs the physicochemical properties of the erythrocyte membrane and further leads to the occurrence of anemia and a reduction of the lifespan. In response, the body activates compensatory reactions directed at a renewal of the red blood cell pool and an increase in tissue oxygenation. In this study the influence of Agaricus brasiliensis and Ganoderma lucidum medicinal mushroom mycelia on the erythron system of control and streptozotocin (STZ)-induced diabetic rats were investigated. Wistar outbred white male rats were intraperitoneally injected with saline (control rats) or STZ (50 mg/kg, DM rats) and orally treated with placebo or submerged culture mycelium powder (1 g/kg/day) for 2 weeks. Peripheral blood erythrocytes were collected. Hypoglycemic effects of A. brasiliensis and G. lucidum occurred in the diabetic rats, as evidenced by decreased blood glucose and glycosylated hemoglobin concentrations. In STZ-diabetic animals treated with submerged culture mycelium powder, an increase in the number of erythrocytes in the bloodstream (an antianemic effect), erythrocyte resistance to acid hemolysis, and the normalization of fetal hemoglobin concentrations, along with the intensification of erythropoiesis were observed. In conclusion, our results suggest that in diabetic animals A. brasiliensis and G. lucidum have therapeutic effects that manifest in hypoglycemic and antianemic action.

Under conditions of chronic hyperglycemia there is dysregulation of ion homeostasis, violation of redox metabolism and functioning of membrane enzymes, as well as changes in the structural and functional states of erythrocyte membranes. As a result, the aggregation ability of erythrocytes increased and their deformability decreased. These changes lead to complications to microcirculation blood flow and provoke the development of vascular complications caused by diabetes mellitus. This study investigated the effect of the medicinal mushrooms Agaricus brasiliensis and Ganoderma lucidum on the structure of carbohydrate determinants of surface membrane glycoconjugates of rat peripheral blood erythrocytes under both normal conditions and streptozotocin-induced diabetes mellitus. The research was carried out using Wistar outbred white rats. Diabetes was induced by streptozotocin intraperitoneally injected once at a dose of 50 mg/kg body weight. The mushroom preparations were orally administered at a dose of 1 g/kg for 14 days. The treatment of diabetic rats by submerged culture mycelium powder restored the physiological balance between sialylation and desialylation processes, renewed the membrane surface charge of red blood cells, normalized aggregation properties, and caused the structural recovery of oligosaccharide chains of erythrocyte membrane surface glycoconjugates. The discovered changes show an improvement in the erythrocyte functional state and rejuvenation of their population caused by biologically active compounds of the studied medicinal mushrooms.

Excessive glucose concentrations in blood and cells promote the intensification of auto-oxidation. This is one of the mechanisms through which free radicals form in hyperglycemia. As a result of hyperglycemia, oxidative stress develops and lipid peroxidation (LPO) is enhanced. Erythrocytes are particularly susceptible to reactive oxygen species and LPO, which can violate cell functions. This article describes the analysis of the influence of mycelia from the medicinal mushrooms Agaricus brasiliensis and Ganoderma lucidum on the enzymatic link of the antioxidant system in rat erythrocytes under streptozotocin-induced diabetes mellitus. Oxidative stress was strengthened in red blood cells of diabetic rats, as evidenced by decreased activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, and by increased amounts of thiobarbituric acid-positive products, which are markers of LPO. Administration of A. brasiliensis and G. lucidum submerged cultivated mycelial powder to animals with streptozotocin-induced diabetes restored superoxide dismutase, catalase, and glutathione peroxidase activity and reduced the amounts of thiobarbituric acid-positive products to control values, but did not affect the activity of glutathione reductase.

Increase of nitric oxide production resulted in the development of oxidative-nitrosative stress that is considered to be an etiological cause of many diseases, including diabetes mellitus (DM). Recently, it was found that red blood cells (RBCs) are able to produce nitric oxide (NO), and due to the ability of hemoglobin to bind to nitric oxide, are the main depot of NO. Medicinal mushrooms are widely used in the correction and treatment of many diseases, including diabetes. Our previous results showed that Agaricus brasiliensis and Ganoderma lucidum have hypoglycemic effects and improve the functional state of RBCs. In this study, the influence of submerged cultivated mycelium powder (SCMP) of the abovementioned mushrooms on the red blood cells L-arginine/NO system of streptozotocin-induced DM rats was investigated. Wistar outbread white rats were used in the study. Streptozotocin was intraperitoneal injected one time at a dose of 50 mg/kg body weight. Mushroom preparations were orally administered at a dose of 1 g/kg/day for 14 days. We showed that administration of medicinal mushrooms SCMP to diabetic animals caused restoration of NO-synthase activity, normalized nitrite content (in case of A. brasiliensis), and led to nitrate growth. Therefore, treatment with mushroom mycelia normalizes the production of nitric oxide to physiological values.