Vol 27, No 10 (2024)

Introduction. Plant-based drugs and medicines are used in medical practice for the treatment of a wide range of diseases, including gastrointestinal diseases: chronic gastritis and/or gastroduodenitis, gastric and duodenal ulcers.

The purpose of the work is to study and evaluate of anti-ulcer, anti-inflammatory and immunomodulatory activities of jujuba fruits (Ziziphus Jujuba Mill.) polyextract.

Material and methods. Experimental samples of CO₂ extract, alcoholic extract, thick extract, dry extract and polyextract of Ziziphus Jujuba Mill fruits were studied. Biological activity of the samples was evaluated using a specific enzyme biotest system based on inducible NO synthase in vitro. The acute toxicity affecting the exudative phase of the acute reaction was studied in a model of formaldehyde edema of the paw of mice, as a result of screening the polyextract of jujube fruits which has the most pronounced pharmacological activity, and also studied its antiulcer effect on an ethanol model of damage to the gastric mucosa in rats.

Results. As a result of screening studies using a specific enzyme biotest system based on inducible NO synthase, immunomodulatory properties were discovered in all experimental jujube fruit extracts. Polyextract of jujube fruits demonstrated the most pronounced immunomodulatory therefore it was chosen for further pharmacological studies. In accordance with the classification of toxicity of chemical substances according to the standards of the Russian Federation, polyextract of jujube fruits is a low-toxic substance. The polyextract has an anti-inflammatory effect, it suppresses the development of the exudative phase of inflammation in a model of formaldehyde edema of mouse paws. A significant gastroprotective effect of the polyextract of the fruits of Ziziphus Jujuba Mill was revealed in an experimental model of rat gastric ulcer caused by the administration of ethanol.

Conclusions. Polyextract of jujube fruits has a wide range of biological activity: immunomodulatory, anti-inflammatory, antiulcer, and is also a low-toxic substance. This extract is promising for further in-depth study and the creation of a new effective herbal medicine based on it.

Introduction. Primary bone sarcomas are relatively rare neoplasms. They occur predominantly in adolescents and young adults, are characterized by an aggressive clinical course and a high metastatic potential, have a poor prognosis. In this regard, the problem of stratifying the risk of metastasis and death in order to select the optimal treatment tactics always remains relevant. The study of such markers as endostatin, vascular endothelial growth factor (VEGF), insulin-like growth factors IGF-1, IGF-2 as potentially informative predictors of survival in patients with bone sarcomas is pathogenetically determined by their involvement in the processes of tumor growth and metastasis.

Aim – to analyze the relationship between pre-treatment serum levels of endostatin, VEGF, IGF-1 and IGF-2 with overall survival rates in patients with bone sarcomas.

Material and methods. An analysis of overall survival rates was carried out in 134 patients with malignant bone tumors aged from 1 to 73 years (Me=27.0 years; Q₁–Q₃: 18.0 – 43.0 years), among them 87 men (64.9%) and 47 women (35.1%). All patients comprised 4 groups: osteosarcoma (n=58), undifferentiated pleomorphic sarcoma (n=5), Ewing sarcoma (n=29), chondrosarcoma (n=42). In all of them, before the start of specific antitumor treatment, the levels of endostatin, VEGF, IGF-1, and IGF-2 in the blood serum were determined using enzyme immunoassay. The follow-up period ranged from 1 to 229 months (Me=23.0 months; Q₁–Q₃: 10.0–121.0 months). To analyze overall survival, life tables and Kaplan–Meier curves were constructed. The effect of the studied serum markers on survival rates was assessed using the logrank test and Cox proportional hazards regression model.

Results. During observation, death occurred in 51 patients (38.1%). In the group of deceased patients, serum levels of endostatin and IGF-2 were statistically significantly increased compared to the group of surviving patients (p<0.001 and p=0.011, respectively). Kaplan-Meier survival analysis using the logrank test revealed statistically significant differences in overall survival between the four groups of patients with different serum levels of endostatin, IGF-1 and IGF-2. The Cox regression method established the prognostic significance of endostatin as a predictor of overall survival (HR=1.012; p=0.013).

Conclusion. Endostatin, IGF-1, IGF-2 can serve as predictors of overall survival of patients with bone sarcomas.

Introduction. Parkinson's disease (PD) is a chronic neurodegenerative disease of the central nervous system with accumulation of alpha-synuclein and degeneration of nigrostriatal neurons. A number of studies have shown that one of the links in the pathogenesis of PD may also be microdamage of blood vessels. However, how these changes affect intercellular contacts of endothelial cells and the permeability of the blood-brain barrier has not yet been studied.

The aim of the study. To study the permeability of the blood-brain barrier and the level of proteins of intercellular contacts in experimental toxic parkinsonism.

Material and methods. The study was performed on male Wistar rats weighing 280-320 g. Toxic parkinsonism was modeled by subcutaneous administration of rotenone at a dose of 2.5 mg/kg 1 time per day for 7 and 28 days. Dopamine levels were determined in the striatum and midbrain by the ELISA method, and the level of intercellular contact proteins occludin, E-cadherin and ZO-1 were analyzed in the cerebral cortex by the western blot. The permeability of the blood-brain barrier was assessed by penetration of Evans blue dye into brain tissue.

Results. The administration of rotenone caused the development of experimental parkinsonism, which manifested itself in a typical clinical picture and a decrease in dopamine levels in the striatum and midbrain on days 7 and 28 of administration. At the same time, there was a decrease in the relative amounts of occludin, E-cadherin and ZO-1. These biochemical changes led to the permeability of the blood-brain barrier to the Evans blue dye on the 7th and 28th days of the experiment, which indicates an increase in the permeability of the blood-brain barrier.

Conclusion. Thus, in rotenone-induced parkinsonism, the permeability of the blood-brain barrier increases, which is caused by a decrease in specific tight junction proteins that form the connection between endothelial cells and the perivascular microenvironment. The results obtained make a significant contribution to modern understanding of the pathogenesis of Parkinson's disease and allow to identify new approaches to its treatment.

Introduction. To date, there has been an increase in thyroid diseases mediated by a violation of regulatory mechanisms on the part of the central structures of the hypothalamic-pituitary-thyroid system. Numerous scientific studies have revealed that the emerging thyroid imbalance in thyroid diseases causes the development of metabolic syndrome, disorders of the cardiovascular system, as well as neuropsychic changes, which are often the first clinical manifestations of thyroid pathology. The current direction today is the study and development of means of correction of possible neuropsychic disorders. Of interest are the compounds of the peptide structure, on the basis of which effective drugs with a wide variety of pharmacological properties are being synthesized today. It has been proven that peptide compounds have neurotropic, psychotropic, anxiolytic, and other pharmacological effects due to their effect on the functional activity of neurotransmitter systems.

The aim of the study was a screening study of the psychotropic activity of peptide compounds in conditions of hypofunction of the thyroid gland.

Material and methods. The study was conducted on male rats divided into groups: I-th – control animals; II-th – individuals with induced hypothyroidism; III, IV, V, VI, VII and VIII-th – animals treated with hypothyroidism, respectively, Thr-Lys-Pro-Arg-Pro-Gly-Pro, ACTH(4-7)-Pro-Gly-Pro, ACTH(6-9)-Pro-Gly-Pro, Pro-Gly-Pro, Pro-Gly-Pro-Leu, Arg-Pro-Gly-Pro, Pro-Gly-Pro-Val and Met-Thr-Lys-Pro-Arg-Pro-Gly-Pro doses 87; 87; 89; 33; 44; 42; 42; 88 mcg/kg/day, which were 1/10 of the molecular weight of the studied substances. The psychotropic activity of the studied peptides was studied using the Open Field test.

Results. It was found that in the conditions of experimental hypothyroidism, there is an inhibition of motor and exploratory activity against the background of an increase in anxiety levels (duration of freezing, grooming reactions and the number of defecations). The studied peptide compounds had a corrective effect to varying degrees on the psychoemotional state of laboratory animals in conditions of hypofunction of the thyroid gland.

Conclusions. The results of a screening study in a number of regulatory peptides indicate that the compounds ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro have the most pronounced psychotropic activity in relation to behavioral indicators in the Open Field test under conditions of experimental hypothyroidism.

Introduction. A new approach in the bladder diseases treatment is an intravesical instillation of drugs. However, the low therapeutic effectiveness and painfulness of the instillation procedure are significant limitations of this method. Often, therapy for chronic cystitis comes down to repeated drug instillation into the bladder, which can lead to irritation of the urethral canal and re-infection.

Purpose of the study – an approach to the treatment of chronic cystitis by a combination of the local delivery - intravesical instillation, and advanced materials science technologies - emulsion microgels.

Materials and methods. Hyaluronic acid (HA) was encapsulated in emulsion microgels based on whey protein isolate. To study the therapeutic effect, experimental animals were divided into 3 groups (5 pieces each): without therapy; with encapsulated HA therapy; with therapy of HA solution. Chronic cystitis modeling was carried out by intraperitoneal administration of a cyclophosphamide solution. For groups of the animals receiving therapy, intravesical instillation of HA in encapsulated and free forms was carried out four times on days 6, 10, 14 and 18 after the initiation of cystitis. The therapy effectiveness was assessed using classical histological analysis.

Results. This work demonstrates the effectiveness of chronic cystitis therapy with hyaluronic acid immobilized in mucoadhesive carriers – emulsion microgels. Histological analysis confirmed a significant topical therapeutic effect in animals with intravesical administration of microgels with hyaluronic acid.

Conclusions. The proposed strategy combines local delivery and the use of microcontainers containing a drug, which can be successfully used for local therapy of a wide range of bladder diseases.

Intoduction. Ginkgo biloba (L.) are relict plants characterized by a limited area of growth, the valuable biomass of which is able to accumulate unique secondary metabolites that do not have synthetic analogues. Based on extracts of the leaves of ginkgo biloba, which have a nootropic effect. biologically active additives and medicines are produced – Tanakan, Bilobil, Ginkor gel, etc.. Plants of the genus Ginkgo grow in specialized microecological niches that limit their natural distribution area. It is known that biotic stress is one of the main environmental factors limiting the introduction of valuable plant species – possible sources of production of unique metabolites. Limiting environmental factors have a direct impact on the growth, development and productivity of secondary plant metabolism. Stress-resistant and highly productive plants can be created using cell biotechnology methods, in particular, in vitro cell selection, which is carried out on a callus culture. Therefore, at the first stage, it is necessary to develop in vitro technology for the rapid production of well-proliferating callus tissue with an increased content of secondary metabolites.

Purpose of the study. To study the effect of the vegetation and photoperiod, endogenous polyphenols on the formation of the callus tissue of sequoia (Ginkgo biloba (L.)) in vitro.

Material and methods. The object of the study was Ginkgo biloba (L.) plants. Callus tissue was obtained from segments of leaf blades that were isolated from intact plants. Explants were cultured on WPM nutrient medium containing BAP 2.0 mg/l and 2.0 mg/L 2,4-D. The localization of phenolic compounds was studied in Ginkgo leaves, as well as in callus tissue obtained under different lighting conditions. To do this, histochemical methods were used: for the sum of phenolic compounds, the material was stained with 0.08% Fast Blue reagent raster, a reaction with vanillin reagent in hydrochloric acid vapor was used to study the localization of flavans (catechins and proanthocyanidins).

Results. The intensity of callus tissue formation, its consistency and color were significantly influenced by the growing season and the applied lighting regime. A well-proliferating callus tissue of light yellow color was obtained by cultivation with no light source. At a 16-hour photoperiod, a dark brown callus tissue with green inclusions was formed, the growth of which was inhibited during cultivation. Explants collected in spring and summer had the best proliferative activity. As a rule, the formation of callus tissue occurred in places of minor localization of phenolic compounds. In initiated callus cultures grown in the dark, the content of cells with phenolic compounds was lower than that of callus obtained in the presence of lighting. Extracts of G. biloba L. callus cultures they exhibit low cytotoxicity and can be widely used as a safe raw material for phytopharmacognosy.