Hypoglycemic and antioxidant properties of extracts of medicinal plants Galega officinalis L. (aboveground part) and yacon (Smallanthus sonchifolius Poepp. & Endl.) (leaves) as potential sources of biologically active substances with antidiabetic action have been studied. The pronounced hypoglycemic effect of Galega officinalis extract, devoid of alkaloids, at a dose of 600 mg/kg in experimental diabetes mellitus (DM) has been proven. The established effect is evidenced by a decrease in the concentration of glucose and glycosylated hemoglobin in the blood, increase glucose tolerance of cells, increase C-peptide and insulin content in the plasma of rats’ blood. The effective hypoglycemic effect of the extract in the studied pathology was confirmed by histological examination of the pancreas. The cytoprotective effect of the studied extract on pancreatic cells at a dose of 1200 mg/kg was experimentally confirmed. In the standard cut area, an increase was found in the number of Langerhans islets, their average area, diameter, volume, and a number of β-cells relative to these indicators in animals with diabetes. Comparative screening of the antioxidant properties of 30, 50, 70, and 96% water–ethanol extracts of yacon indicates the highest potential of 50% water-ethanol extract to block free radicals in in vitro model experiments. The non-alkaloid fraction of Galega officinalis extract showed moderate antioxidant activity and was inferior to yacon extract in its ability to neutralize reactive oxygen species (ROS) and bind metal ions of variable valence. The level of antioxidant potential of the studied extracts is due to differences in the quantitative content of compounds of phenolic nature in their compositions. The obtained data on the biological effects of Galega officinalis extract on the structural and functional state of β-cells of the pancreas and antioxidant properties of Galega officinalis and yacon extracts substantiate the prospects of using these plants to create antidiabetic medicines and functional foods based on them.

An impaired leukocytes function is the factor causing the susceptibility of patients with diabetes mellitus to infections. The outmost importance for the understanding of the immunological processes involved in diabetes pathogenesis is to give the characteritics of the immunological profile and changes therein, during the course of desease. Long-used in folk medicine to treat diabetes Galega officinalis L. has been chosen for the correction of the immune system dysfunction. The experiments were conducted on male Wistar rats. Fractionation of bone marrow cells suspension was performed in a three-layer ficoll–sodium amidotrizoate density gradient. The lymphocytic-granulocytic cells proliferative activity was studied using enzyme immunoassay with 5-bromo-2′-deoxyuridine (BrdU). For staining of bone marrow preparations May-Gruenwald-Romanowsky-Giemsa (Pappenheim) method was used. To evaluate the content of cationic proteins and myeloperoxidase in neutrophilic leukocytes cytochemical studies were performed. Content of tumor necrosis factor alpha was carried out by immuno-enzymatic analysis. Lymphocytes apoptosis was examined by fluorescent analysis using annexin V. Diabetes mellitus development was accompanied with violation of neutrophils and lymphocytes proliferation, increased activity of myeloperoxidase and enhanced apoptosis process. Administration of Galega officinalis extract under the condition of diabetes promotes the restoration of neutrophils bone marrow pool and the reduction of lymphoblasts number and causes inhibition of the lymphocytes apoptosis process. Investigated medicine has a pronounced immunocorrective effect under the conditions of diabetes mellitus and can become the basis for creating a new generation of antidiabetic drugs.

The article describes the effect of alkaloid-free fraction of the Galega officinalis extract (AFFGE) on the aggregation ability of immunocompetent blood cells, as well as on the process of actin polymerization and structural rearrangements among sialylated glycoconjugates of the peripheral blood leukocyte membranes of rats in the norm and under experimental diabetes mellitus (EDM) conditions. The flow cytometry method (using phalloidin labelled with fluorescent tetramethyl rhodamine-5-isothiocyanate (TRITC)) and the western blot analysis have allowed us to detect an increase in the rat leukocyte F-actin content in the event of diabetes mellitus, which indicated changes in the structural and functional properties of the leukocytes and their preactivation phase. A quantitative analysis of the total polymerized actin pool redistribution between its constituent fraction (represented by cytoskeletal filaments) and short actin filaments has shown that, against an increase in the total F-actin level, the number of actin filaments of the cytoskeleton decreased and the content of short actin filaments increased in leukocytes of animals with EDM. The use of sialylated lectins has allowed a conclusion to be made on the study of the pathology that the number of exposed oligosaccharide determinants on leukocyte membrane, the structure of which contained N-acetyl-β-D-glucosamine and sialic acid residues, increased, whereas the number of sialic acid-containing surface glycoconjugates bound to subterminal galactose residues by α2→3 and α2→6-glycoside bonds decreased. The administration of AFFGE to diabetic animals led to an increase in the content of F-actin and short filaments of the leukocyte cytoskeleton and a reduction in the lectin-induced leukocyte aggregation. The correction effect of the studied extract on the functional state of leukocytes can be realized through the action on the processes underlying the formation of the actin cytoskeletal elements and due to the quantitative redistribution of leukocyte membrane glycoconjugates with different structures of carbohydrate determinants, such as, due to a decrease in the exposure of N-acetyl-β-D-glucosamine residues and an increase in the exposure of sialic acids bound to subterminal galactose residues by α2→3 and α2→6-glycoside bonds.

Background. Diabetes mellitus intensifies non-enzymatic glycosylation (glycation) of biomolecules under conditions of chronic hyperglycemia and facilitates accumulation of advanced glycation end products. Disorders of the cells of various tissues are caused by binding of advanced glycation end products to the corresponding receptors, the level of receptors for advanced glycation end products increases under conditions of hyperglycemia. The interaction between receptors for advanced glycation end products and advanced glycation end products leads to the formation of excessive reactive oxygen species, changes in intracellular signaling, gene expression, increased secretion of pro-inflammatory cytokines and contributes to the development of diabetic complications. The search for factors of natural origin that will slow down the development of specific complications of diabetes, determines the feasibility of studies of the corrective ability of biologically active substances isolated from medicinal plants for the process of glycation of proteins in diabetes. Materials and methods. Experimental diabetes mellitus was induced by intraperitoneal administration of streptozotocin. Separation of blood leukocytes was performed in Ficoll density gradient. To determine the extent of advanced glycation end products and receptor for advanced glycation end products in leukocyte immunoperoxidase labeling was performed. Results. A decrease in the content of advanced glycation end products in leukocy­tes under conditions of experimental diabetes mellitus was found. The obtained data indicate a possible contravention of glucose uptake by leukocytes in the studied pathology. At the same time, an increase in exposure to the receptor for advanced glycation end products leukocyte membranes in response to chronic hyperglycemia has been demonstrated. The ability of alkaloid free fraction of Galega officinalis extract to reduce the content of receptors for end products of glycation on the membranes of immunocompetent cells in diabetic animals has been confirmed, which may be due to the presence of biologically active substances with hypoglycemic action in its composition. Conclusion. Corrective effect of alkaloid free fraction of Galega officinalis L. extract on the content of receptor for advanced glycation end products in diabetes mellitus is mediated by its normalizing effect on carbohydrate metabolism.

Introduction. Dyslipidemia is a significant risk factor for cardiovascular disease in patients with diabetes mellitus, especially of type 2. The search for biologically active compounds derived from natural products capable of correcting lipid metabolism is a promising direction in the development of effective and safe dyslipidemia therapy. This study compared the hypoglycemic and antilipidemic potential of the non-alkaloid extract of Galega officinalis and the official herbal medicinal product Arfazetyn under experimental diabetes mellitus. Materials and Methods. Experimental diabetes mellitus was induced by intraperitoneal administration of streptozotocin. The study utilized a non-alkaloid fraction of Galega officinalis extract stabilized with biosurfactants – products of Pseudomonas sp. PS-17 biosynthesis – and the official herbal preparation Arfazetyn. To assess the hypoglycemic effect of the G. officinalis extract and Arfazetyn, glycated haemoglobin and blood glucose levels were measured, an oral glucose tolerance test was performed, and the area under the glycemic curves was calculated. To evaluate the corrective effect of the investigated herbal preparations on lipid metabolism, lipid profile analysis was conducted (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides). Results. The results indicate that the non-alkaloid fraction of Galega officinalis extract effectively lowers blood glucose and glycated hemoglobin levels to within the physiological range, while also improving glucose tolerance under experimental diabetes mellitus conditions. Moreover, this extract demonstrated a higher hypoglycemic potential than the official herbal medicinal product Arfazetyn. Additionally, administration of the G. officinalis extract contributed to normalizing total cholesterol, low-density lipoprotein cholesterol, decreasing triglycerides, and increasing high-density lipoprotein cholesterol content. Conclusion. The established hypoglycemic potential of the non-alkaloid fraction of Galega officinalis extract, its ability to correct manifestations of dyslipidemia under experimental DM, confirms its therapeutic potential in managing lipid disorders and reducing associated cardiovascular risks.

Oxidative-nitrative stress induced by hyperglycaemia plays a key role in the development of complications of diabetes mellitus (DM), in particular, nephropathy. Thus, it is important to study the antioxidant activity of various compounds, including natural antioxidants of plant origin, to reduce the risk of diabetic complications. The combination of antioxidants and traditional antidiabetic drugs will provide more effective glycaemic control, and naturally occurring drugs have fewer side effects. The present study aims to investigate the corrective effect of alkaloid-free fraction (AFF) from Galega officinalis extract on the markers of oxidative and nitrative stress in the experimental diabetes mellitus (EDM) in the rat kidney. In this study, we used medicinal plant (Galega officinalis L.). This plant has long been used in folk medicine to treat mild forms of diabetes, but the content of toxic alkaloids limits the possibility of its use in therapeutic amounts. AFF enriched with components with potential hypoglycemic and antioxidant activity, and demonstrating no toxicity, was obtained from the aerial parts of Galega officinalis. An increase in the levels of stable NO metabolites – nitrite and nitrate anions and the activity of inducible NO-synthase (iNOS) was observed in the kidneys of rats, which, along with elevated levels of TBARS (thiobarbituric acid reactive substances), indicates the development of oxidative-nitrative stress under experimental diabetes mellitus (EDM) conditions. A reduction in nitrite and nitrate anion content, NOS activity, and TBARS levels was noted in diabetic animals treated with the AFF from Galega officinalis extract for 14 days. The obtained results confirm the antioxidant properties of AFF from G. officinalis extract under diabetic conditions. The main active components of G. officinalis extract responsible for its antioxidant activity are phytol, flavonoids, and phenolic acids. The combination of hypoglycemic and antioxidant effects of AFF from G. officinalis extract may not only contribute to the compensation of hyperglycemia but also reduce the risk of developing diabetes-associated complications such as neuropathy, nephropathy, and retinopathy caused by oxidative-nitrative stress.