Problems of Biological Medical and Pharmaceutical Chemistry

Introduction. Today, one of the reliably known causes of mortality in the Russian Federation is diseases of the cardiovascular system, a significant part of which is associated with atherosclerotic disease. Combination therapy for diseases of the cardiovascular system includes, among other things, the use of modern lipid-lowering drugs, the use of which is often limited due to their pronounced side effects. In this regard, it seemed appropriate to search for new compounds of natural origin that potentially have lipid-lowering activity with minimal side effects. According to the scientific literature, natural phenolic compounds, namely substances from the group of flavonoids and isoflavonoids, have a set of such characteristics. In this regard, steelgrass (Ononis arvensis L.), the chemical composition of which is extremely rich and diverse in terms of flavonoids and isoflavonoids, can be a rather promising source for searching and screening compounds with a given activity.

The aim of the study. The purpose of the work was to study and predict the hypolipidemic activity of flavonoids and isoflavonoids of Ononis arvensis L. using in silico methods.

Material and methods. The objects of the study were the structural formulas of flavonoids and isoflavonoids of field steelhead. Calculation of molecular properties was carried out using the Molinspiration chemoinformatic software. Computer prediction of lipid-lowering activity was carried out using the PASS-online service. Molecular docking was performed using the CB-Dock2 services for blind docking and Webina 1.0.5 for active site docking. Hepatotoxicity, mutagenicity and cytotoxicity of the analyzed biologically active substances were studied using the ProTox-II resource.

Results. As a result of in silico studies, it was found that most of the studied flavonoids and isoflavonoids correspond to the Lipinski rule and the drug-likeness concept. In addition, for all studied biologically active substances, activities associated with a decrease in lipid fractions in the body were predicted. The results of molecular docking indicate that all analyzed compounds are capable of potentially inhibiting the enzyme HMG-CoA reductase, which makes it possible to predict the required lipid-lowering effect. Studying the toxicity of the research objects, most of them in silico demonstrated a high level of safety.

Conclusions. The prospects for further research on the development of targeted technology for obtaining herbal preparations from steelhead, enriched with flavonoids and isoflavonoids, as well as subsequent tests to confirm hypolipidemic activity in in vitro and in vivo experiments are shown.

Introduction. One of the most important issues in the development and improvement of pharmacy is the creation of original and increasing the effectiveness of existing dosage forms. At the same time, there is justifiable interest in the group of application dosage forms (ADF), which have many advantages, both biopharmaceutical and technological and economic in nature. At the same time, the most significant and promising within this group are dosage forms such as gels and films.

Purpose of the study – development of optimal composition, adhesive gel technology, pharmacological confirmation of effectiveness on a model of intestinal anastomosis.

Material and methods. To obtain an adhesive gel, compositions based on Na-CMC (0.5–1.5%), Na-alginate (0.5–1.5%) and chitosan (1–3%) were prepared. The osmotic capacity of the gels was studied using a model of dialysis through a semipermeable membrane. The adhesive properties of the gel were determined on an experimental model of intestinal anastomosis by the time of localization of the film-gel complex at the site of application. The biodegradation properties of the film-gel complex were also studied in in vitro and in vivo experiments.

Results. A 1.5% gel based on Na-CMC has a greater capacity compared to other prototypes, capable of absorbing up to 12.56% of moisture from its own weight. Gel based on Na-alginate (1.5%) absorbs up to 10.20%, and chitosan (3.0%) – up to 11.05% moisture. The “film-gel” complex based on chitosan gel (3.0%) did not migrate from the site of application within 128 hours, which indicates its satisfactory adhesive properties, since the time during which the complex was at the site of localization corresponds to the critical time the period during which coronary artery failure most often occurs. The film-gel complex biodegraded in the blood plasma of rats within 136 hours, and remained in the abdominal cavity of rats at the site of application for up to 7 days.

Conclusions. Comparative studies of various models of adhesive gels obtained on different bases were carried out: Na-CMC (1.5%), Na-alginate (1.5%) and chitosan (3.0%) and showed the advantages of a gel based on chitosan in relation to its ability to ensure film fixation at the application site.

Intriduction. Currently, the antibiotic resistance development in pathogenic microorganisms remains a global problem. To solve this problem, an active search and development of new antimicrobial drugs, including those of plant origin, is underway. In the many years course of experience in this area, methods used to determine antimicrobial activity are being developed and improved, however, not all of them are suitable for determining the activity of biologically active substances of plant origin.

The purpose of the study. To summarize information about existing methods for determining antimicrobial activity under in vitro experimental conditions.

Material and methods. The article is based on publication materials from the PubMed and E-library databases, search.rsl. The literary search was carried out by keywords: antimicrobial activity, antibacterial effect, antibiotic, herbal preparations. The review includes articles that are relevant to the research topic and have been published over the past 10 years.

Results and discussion. The article describes the main methods for determining antimicrobial activity in vitro and determines the possibility of using these methods in relation to herbal remedies.

Conclusions. The findings indicated that the choice of the research method should depend primarily on the object under study and the type of microorganism in respect of which the activity is determined. Most of the developed and widely used methods for determining antimicrobial activity do not allow an adequate assessment of the activity of herbal remedies. Thus, when working with herbal remedies, the methods of double serial dilutions in liquid nutrient media with the use of indicators and the developing direction of activity research on biofilms can be considered the most accurate.

The aim is to assess the effect of the opioid peptide dalargin on the behavioral responses of laboratory animals under the conditions of experimental alloxane diabetes mellitus.

Material and methods. The experiment was performed on nonlinear white male rats weighing 280-290 g. Laboratory animals were divided into several groups: 1 – control group, which received water for injection daily by intraperitoneal administration (control), 2 – animals with alloxane diabetes mellitus; group 3 – diabetic individuals treated with dalargin for 21 days intraperitoneally at a dose of 100 mkg/kg/day starting one month after alloxan administration. Diabetes mellitus was modeled by intraperitoneal administration of alloxane to pre-starved animals for 24 hours at a dose of 100 mg/kg once (dose worked out in preliminary studies). Assessment of the severity and dynamics of individual behavioral acts, as well as the level of emotional-behavioral reactivity of animals, was carried out using psychopharmacological tests: "Raised cruciform labyrinth" and "Dark light chamber."

Results. When dalargin was administered to animals under the conditions of alloxane diabetes mellitus, an increase in motor activity and cognitive activity was noted, which indicated a decrease in anxiety that was observed during the development of experimental diabetes mellitus.

Conclusion. Based on the results obtained from the study of the effect of the opioid peptide dalargin on the behavioral responses of laboratory animals under the conditions of experimental alloxane diabetes mellitus, it was found that the investigational drug has psychocorregative, antidepressant and anxiolytic effects.

Intriduction. Changes in oxidative balance and lipid metabolism have the leading role in performance limitation, adaptation and maladaptation to physical activity. It is especially important to analyse the direction of metabolic changes at the subcellular level.

The aim of the study is to examine the state of oxidative balance and cholesterol metabolism in muscle tissue at moderate and maximal swimming load.

Material and methods. A comprehensive study of indicators for free-radical oxidation (content of diene conjugates, TBA-active products, chemiluminescence intensity), antioxidant defense (total antioxidant activity, antiradical activity) and cholesterol metabolism in tissues of heart muscle and thigh muscle of white male rats at moderate and maximum swimming load was carried out.

Results. The patterns of metabolic changes in muscle tissue depending on the intensity of muscular work have been established: these are the forms of compensated oxidative stress at moderate and decompensated at maximum load, against the background of decreasing cholesterol content. In cardiac tissue oxidative stress phenomena were less expressed, and changes in cholesterol content were multidirectional: a tendency to decrease at moderate load and a significant increase at maximum load.

Conclusion. The reduction of antioxidant defence resources and intensification of free-radical oxidation reactions constitute one of the leading mechanisms for metabolic disorders due to extreme physical load, which is confirmed by reliable changes in the studied parameters. The complex study of indicators characterizing the processes of free-radical oxidation, antioxidant protection and cholesterol content is an informative criterion for the influence of physical exercise on the organism. The obtained data allow us to recommend the inclusion of antioxidants in the complex prevention and therapy of acute physical overstrain.