ABSTRACT
According to the current understanding, the hyperactivation of platelets may lead to increased intravascular coagulation and thrombosis. Today a relevant issue is the search for new anti-thrombotic agents that are able to modulate the activity of platelet receptors, thus, influence the processes of activation and aggregation of platelets. The aim of this study was to investigate the effects of newly synthesized thiosulfonate derivatives on platelet aggregation. The activity of the compounds was tested in vitro using platelet-rich plasma. As a result of the screening test, structural formulas of four agents with high antiaggregative activity were established. These compounds inhibited ADP- and collagen-induced platelet aggregation in a dose-dependent manner. Two of these compounds were shown to be more effective inhibitors of aggregation induced by ADP (IC50 - 8-10 µM), as well as collagen (IC50 - 1.5-2.0 µM).
Subject(s)
Blood Platelets/drug effects , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation/drug effects , Thiosulfonic Acids/chemical synthesis , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Drug Discovery , Esters , Molecular Structure , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology , Platelet-Rich Plasma/cytology , Rabbits , Structure-Activity Relationship , Thiosulfonic Acids/chemistry , Thiosulfonic Acids/pharmacologyABSTRACT
The influence of the aqueous pods extract of kidney bean (Phaseolus vulgaris) on indicators of carbohydrate metabolism under the condition of experimental type 1 diabetes in rats was studied. It was shown that long-term oral administration of the extract at a dose of 200 mg/kg to rats leads to the decreasing of blood glucose and glycosylated hemoglobin in the background of chronic hypoinsulinemia conditions. The use of studied extract led to an increase of glycogen synthase activity in rat muscle cells and hexokinase activity in rat liver cells under the conditions of type 1 diabetes. It was estimated that administration of the aqueous extract to control rats and animals with studied model of diabetes increases GLUT-4 protein content in muscle tissue. Thus, the mechanisms of P. vulgaris hypoglycemic action can be related with the ability of the particular phytoconstituents directly effect on key intracellular elements of insulin target tissues carbohydrate metabolism under the conditions of type 1 diabetes.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Phaseolus/chemistry , Plant Extracts/pharmacology , Administration, Oral , Animals , Animals, Outbred Strains , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Female , Gene Expression Regulation , Glucose Transporter Type 4/genetics , Glucose Transporter Type 4/metabolism , Glycated Hemoglobin/metabolism , Glycogen Synthase/genetics , Glycogen Synthase/metabolism , Hepatocytes/drug effects , Hepatocytes/enzymology , Hexokinase/genetics , Hexokinase/metabolism , Hypoglycemic Agents/chemistry , Male , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/enzymology , Plant Extracts/chemistry , Rats , Seeds/chemistry , Streptozocin , Waste Products/analysis , Water/chemistryABSTRACT
The influence of new derivatives of 9,10-anthraquinone with benzoylthiourea, thiazole, triazole and amino acid fragments on the activity of membrane-associated tyrosine kinases was investigated. Inhibitors of protein tyrosine kinase activity of the membrane fraction, as promising agents to search for new potential anticancer agents among the studied compounds, were discovered.
ABSTRACT
Nowadays the problem of insulin resistance, which has close cause-effect relations with obesity, diabetes mellitus type 2, metabolic syndrome, etc., is of urgent importance in medicine. We have revealed bidirectional changes of the IR content in crude membrane and cytosol of the adipose tissue cells in rats under conditions of the long-term high-energy diet. It is possible that reduction of the IR content in the adipose tissue cells has been predetermined by the disruption of lipid bilayer of adipocytes as a result of peroxidation processes activation. Increase in the IR content in the cytosol of cells of this tissue may indicate the activation of synthesis of this protein; however, it is possible that the IR translocation process disorder occurs due to the damage of plasma membrane, preventing the transfer of newly synthesized molecules of the receptor to the membrane and causing their accumulation in cytosol. The obtained results show that the tissues react to the long-term consumption of high-energy food in different ways. Thus, the content of insulin receptors in the plasma membrane of the muscle tissue cells increases, and, on the contrary, it decreases in adipose tissue cells. Such results may indicate that IR development at the late period of the experiment is likely the result of the adipose tissue cells disfunction. The obtained data may be of high significance in understanding the mechanism of the IR development under conditions of the long-term consumption of the high-energy food.
