Research Results in Pharmacology

Cardiotropic medicinal products of plant origin. Prospects for use in modern clinical practice

Nadezhda V. Nesterova — 2025-03-30

Introduction: The aim of the research was to study the current state of use and improvement of the prospects for the using cardiological medicinal products obtained on the basis of medicinal plant raw materials.

Materials and Methods: The work used content analysis, monitoring of scientific articles using the databases PubMed, Scopus, Google Scholar, ResearchGate, analysis of the nomenclature of the State Register of Medicines of the Russian Federation (2024) and the Register of Medicines of Russia (2024).

Results and Discussion: The study revealed that diseases of the cardiovascular system are some of the most common causes of death among the population, with at least 37.7 million people suffering from varying degrees of heart failure alone. Despite the constant growth of the range of medicines for the treatment of cardiovascular diseases, medicinal plants and preparations based on them, which are more often used in complex therapy, still play an important role in their therapy. In this review, we consider drugs derived from medicinal plant raw materials used for the treatment of heart failure and arrhythmia of various etiologies, as the most serious cardiovascular pathologies.

Conclusion: Preparations based on herbal remedies with cardiotropic and antiarrhythmic effects are relevant in the treatment of cardiovascular diseases. Cardiotropic action is characteristic of the group of cardiac glycosides, and antiarrhythmic activity is more pronounced in alkaloids and flavonoid substances. Taking into account the prospects for the use of herbal preparations with cardiotropic effects in the complex therapy of cardiovascular diseases, an important and unsolved problem today remains the problem of their interaction with other drugs, which in the future can be solved by creating artificial intelligence programs that contribute to the formation of optimal prescriptions for a particular patient.

Effect of cyclophosphamide on regulation of heart contractions by means of sodium calcium exchanger

Tatyana A. Berezhnova — 2025-02-25

Introduction: Every year brings in new medications capable to slow or stop proliferation of tumour cells. Unfortunately, in spite of antitumour benefits, new medicines have some side effects that reduce their therapeutic properties.

Materials and Methods: The study was conducted in three series of experiments on 24 whiteWistar rats, both male and female, each weighing 200-250 g. Decapitation of the animal was performed under ether anesthesia with rapid extraction of the heart and perfusion using the Langendorff method. To study NCX in the heart, a perfusion device was used to create a permanent coronary flow. Monitoring the physiological state of the heart when changing the composition of solutions was carried out using a balloon inserted into the left ventricle.Contractions and relaxation of the heart were recorded using an electronic pressure sensor. The parameters were documented and processed using the Zet Lab external module software.

Results and Discussion: In the first series of experiments, the effect of hyposodic solution onthe tone of the left ventricle of the heart stopped by a hyperpotassic medium was studied. The developed technique served as the basis for studying the effect of cyclophosphamide on NCX,accompanied by contraction and relaxation of the heart. Experiments have shown the ability of cyclophosphamide to significantly reduce the rate of the tone increase and the development of contraction force, as well as prolong the relaxation time during NCX.

Conclusion: Cyclophosphamide is able to disrupt the capture of ionized calcium in the cytosolby intracellular Ca-accumulating structures during relaxation of the heart. Unlike controlrecordings, in the presence of cyclophosphamide, repeated relaxations do not occur completely.As a result, each subsequent contraction begins at a higher initial diastole level.

Effect of some compounds from the series of derivatives of cyanothioacetamide with analgesic activity on liver function parameters of rats with chronic administration of paracetamol against the background of alcohol load

Elena Yu. Bibik — 2025-03-28

Introduction: Derivatives of 1,4-dihydropyridines from a series of α-cyanothioacetamide derivatives are a potentially promising class of compounds with analgesic activity.

Materials and methods: The experiment was carried out on 64 white male rats weighing 220-250 g. The rats were divided into 8 groups: intact, control, comparison (thiotriazoline 50 mg/kg) and 5 experimental groups (derivatives of 1.4-dihydropyridine and thiadiazine 5 mg/kg). Acute paracetamol-alcohol liver damage was modeled after two weeks of taking 1 mL of 40⁰ ethanol and paracetamol at a dose of 500 mg/kg.

Results: The total bilirubin level in the control group, compared to that in the intact, increased by 2.88 times, direct bilirubin – by 37.8%, ALT – by 38.85%, AST – by 51.54%, and alkaline phosphatase – by 163%. In the reference group, compared to the intact, the ALT level increased by 44.76%, AST – by 18.11%, alkaline phosphatase – by 19.4%, and AST reduced by 22.06%. In the Mar-014 group, direct bilirubin reduced by 42.7%. In the CV-150 compound group, total bilirubin reduced by 51.6%, AST – by 18.64%, and alkaline phosphatase – by 272.4%. In the TD-0331 group, the AST index increased by 35.7%, whereas alkaline phosphatase decreased by 43.1%. In the CV-131compound group, when compared with the control group, total bilirubin reduced by 75.3%, direct bilirubin – by 10.1%, and AST – by 12%. In the d02-123 group, no indicators exceeded the values of rats in the intact group.

Conclusion: The most pronounced hepatoprotective properties were shown by the compound with the code d02-123.

Homozygous mice with mutant protein FUS[1-359] overexpression: Innovative possibilities for ALS treatment

Nikita S. Zhunusov — 2024-12-30

Introduction: This study investigates a mouse model with overexpression of the mutant FUS[1-359] protein, which can be used to evaluate the effectiveness of gene therapy and other pharmacological interventions for amyotrophic lateral sclerosis (ALS). The model enhances the deeper understanding of the mechanisms underlying disease progression and allows for testing new therapeutic strategies.

Materials and Methods: The study utilized tg_hFUS[1-359] animal lines with a transgenic cassette expressing the human mutant FUS[1-359] protein. Animal groups were formed by crossing hemizygous individuals, and analyses were conducted on lifespan, age of disease manifestation, as well as relative copy number and expression levels of the transgenic cassette.

Results and Discussion: The results demonstrated statistically significant differences in the age of onset of initial disease symptoms between homozygous and hemizygous mice. Differences in the copy number of the transgenic insertion were also identified, revealing that homozygous animals exhibited increased expression of the mutant FUS protein in various structures of the central nervous system, consistent with existing literature on ALS pathogenesis.

Conclusion: Mice with hyperexpression of the mutant FUS[1-359] protein represent a promising genetic model for evaluating therapeutic approaches to ALS treatment. This model exhibits clear phenotypic manifestations of the disease and can be utilized for investigating gene therapy methods.

Validation of a mouse model with Apoe gene knockout

Petr R. Lebedev — 2024-12-30

Introduction: The research focuses on the ApoE-/- transgenic mouse model. This model enhances the understanding of the mechanisms underlying disease progression and allows for the testing of new therapeutic strategies.

Materials and Methods: The study employed ApoE (-/-) knockout mice, which were bred to create cohorts of male mice. These males were divided into two equal groups, receiving either a standard diet or a high-fat diet. Analyses included lipid profile assessments, fasting glucose levels, and evaluation of aortic lesion area.

Results and Discussion: The findings revealed statistically significant differences in the ages at which disease symptoms appeared between the groups. The high-fat diet induced hyperlipidemia, leading to accelerated atherosclerosis in the aorta, aligning with existing literature.

Conclusion: ApoE knockout mice represent a promising genetic model for assessing therapeutic approaches to treat cardiovascular diseases. This model exhibits clear phenotypic manifestations of the disease and can be used for pharmacological correction of endothelial dysfunction.

Assessment of the severity of delayed changes in the state of the neuromuscular system during correction of local cold injury of III-IV degree with pCMV-VEGF165 plasmid preparation in an experiment

Darya A. Kostina — 2025-03-30

Introduction: The relevance of the topic is due to a wide range of clinical manifestations of frostbite, including long-term complications such as neuropathy, chronic pain, and functional impairments. Tissue recovery after frostbite depends on the degree of microvascular damage, and VEGF (vascular endothelial growth factor) is considered a promising agent for stimulating angiogenesis and improving tissue trophism. The aim of the study was to study the effectiveness of the use of a genetic construct – pCMV-VEGF165 plasmid in the correction of delayed complications of cold injury in rats.

Materials and Methods: Local frostbite of III-IV degree was modeled in 18 rats using a neodymium magnet cooled in liquid nitrogen. On days 2 and 7 after the injury, pCMV-VEGF165 (60 µg) was administered to the wound edges. The control group received a placebo. The state of the neuromuscular system was assessed using electromyography on days 28 and 60.

Results and Discussion: In the control group, a significant decrease in the amplitude of the M-response (1.75 times, p=0.001) and an increase in the latency period by 10% (p=0.004) were observed, indicating axonal damage and myelinopathy. The decrement index of the M-response increased (2.2 times), suggesting impaired neuromuscular conduction. In the pCMV-VEGF165 group, the amplitude of the M-response, latency period, and decrement index did not differ significantly from those in the intact animal group.

Conclusion: pCMV-VEGF165 promotes a reduction in the degree of tissue damage and accelerates their regeneration by restoring blood flow, confirming its effectiveness in preventing delayed complications of cold injury.

Effectiveness of the tetrapeptide HAEE: an innovative approach to Alzheimer's treatment in experimentation

Evgenii A. Patrakhanov — 2024-12-30

Introduction: Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized by a progressive decline in cognitive functions. According to the “Alzheimer’s Disease International”, there were 36 million reported cases of AD worldwide in 2009, with projections suggesting an increase to 66 million by 2030 and 115 million by 2050.

Materials and Methods: The study was conducted on three experimental groups consisting of male APPswe/PS1dE9/Blg mice on a mixed genetic background with C57Bl6/Chg animals. Each group included 10 mice. At the baseline (point 0), peptides and drugs were administered to two groups of animals aged 6 months. The treatments were given circadianly every 48 hours without breaks for one month. Subsequently, at point 1 of the experiment, half of the group (n=5) was selected for further histological analysis of the brain. The remaining half did not receive any treatments for one month before undergoing histological examination. Statistical significance between experimental and control groups was assessed using an unpaired Student’s t-test at p<0.05.

Results and Discussion: Histological analysis indicated the efficacy of the tetrapeptide HAEE at a dosage of 50 mg per kg of mouse weight, showing a significant reduction in amyloid plaques in the cerebral cortex and hippocampus of the mice.

Conclusion: The study supports the proposed hypotheses and suggests further investigation into additional drug groups recommended for Alzheimer’s treatment for comparative studies.

The influence of exogenous recombinant HSP 70 on the alteration of membrane stiffness in hippocampal neurons following the modeling of neonatal hypoxic-ischemic injury in mice

Vladimir M. Pokrovsky — 2024-12-30

Introduction: The use of atomic force microscopy (AFM) to investigate membrane stiffness in neurons provides valuable insights into cellular mechanisms and their alterations in response to various pathophysiological conditions. Heat shock protein HSP 70, a component of the cellular stress response system, plays a role in stabilizing the protein structures of cellular organelles. However, studies examining changes in the stiffness of hippocampal neuronal membranes in its presence, particularly following cerebral circulation disturbances, have not been conducted yet.

Materials and Methods: The study was performed on a mixed culture of hippocampal neurons derived from 9-day-old male CD-1 mice, obtained 24 hours after modeling neonatal hypoxia-ischemia. The following groups were formed: Intact culture; HI culture; HI + rhHSP70 10^{-6 M}; HI + rhHSP70 10^{-8 M}; HI + rhHSP70 10^{-9 M}; HI + rhHSP70 10^{-12 M}, with the substance added in dilutions from an initial dose of 0.1 µg/g. The Young's modulus was measured using force spectroscopy, and maps of local stiffness of various surface areas were generated.

Results and Discussion: The neonatal hypoxia-ischemia model resulted in an 18% increase in the stiffness of the neuronal cell surface compared to the control group (p<0.001). The addition of rhHSP70 at concentrations of 10^{-6 M} and 10^{-8 M} to the HI culture led to an increase in membrane stiffness by 20% (p<0.001) and 3% (p<0.0034), respectively, while dilutions of rhHSP70 at 10^{-9 M} and 10^{-12 M} resulted in a decrease in membrane stiffness by 35% (p<0.001) and 22% (p<0.001) compared to the intact group, respectively. In comparison to such in the neuronal culture group after neonatal hypoxia-ischemia modeling, membrane stiffness with the addition of rhHSP70 at 10^{-8 M}, 10^{-9 M}, and 10^-12 M decreased by 17% (p<0.0004), 65% (p<0.001), and 49% (p<0.001), respectively.

Conclusion: Thus, the addition of rhHSP 70 results in a reduction in membrane stiffness in the mixed culture of hippocampal neurons in mice, compared to the intact culture obtained after neonatal hypoxia-ischemia. The AFM method allows for the assessment of how various molecules, such as heat shock proteins (e.g., rhHSP70), influence the mechanical properties of membranes, which may be critically important for the development of new therapeutic agents.

Pharmacological correction of post-contrast acute kidney injury with a functional product based on fermented grape juice

Olesya V. Shcheblykina — 2024-12-28

Introduction: Post-contrast acute kidney injury (PC-AKI) is a serious complication when takingiodine-containing radiopaque agents. The study is aimed at pharmacological correction of PK-AKIwith a functional product obtained from fermented red grape berry juice with a high content of stilbenoids (trans-resveratrol and its glycoside polydatin).

Materials and Methods: The study was conducted on 36 male CD1 mice, 8-10 weeks old,weighing 25±3 g. The animals were divided into 3 groups (n=12): a group of intact animals; a group with PC-AKI modeling; and a group with PC-AKI modeling and preliminary intragastricadministration of a functional product in a volume of 0.1 mL/10 g per animal. A morphologicalassessment of kidney changes was performed, as well as a blood test for creatinine, urea, andalbumin.

Results: Preliminary administration of the functional product to mice led to a statisticallysignificant decrease in creatinine and urea concentrations to 43.5±1.6 μmol/L and 34.5±1.4μmol/L, respectively; the glomerular filtration rate increased to 66.2±4.1 µL/min and the urea/albumin ratio decreased to 1.9±0.03, with mortality also decreasing to 8.3%.

Conclusion: The preventive use of a functional product based on fermented red berry juice inan amount of 0.1 mL/kg of animal effectively reduces the severity of post-contrast acute kidneyinjury in a mouse model.

Pharmacological analysis of the role of kisspeptin-10 in reinforcing mechanisms

Sarng S. Pyurveev — 2025-03-30

Introduction: Behavioral and substance addictions are driven by shared neurobiological mechanisms, often involving the reward system. Kisspeptin-10, a neuropeptide primarily linked to reproductive functions, has emerged as a potential modulator of reward-related behaviors and decision-making. This study explores the effects of kisspeptin-10 on impulsivity, compulsivity, and reinforcement mechanisms.

Materials and Methods: Male Wistar rats were used to assess the effects of kisspeptin-10 on behavior. A conditioned place preference (CPP) test evaluated reinforcement effects at doses of 0.1 mg/kg, 0.5 mg/kg, and 1 mg/kg. A modified Iowa Gambling Task analyzed decision-making and impulsivity under variable reinforcement schedules. The marble-burying test was employed to assess compulsive behaviors. Statistical analysis included one-way ANOVA and Tukey's post-hoc test.

Results and Discussion: Kisspeptin-10 at 1 mg/kg induced a significant CPP response, suggesting reinforcing properties. In the gambling task, kisspeptin-10 enhanced impulsive choices by increasing preference for riskier reinforcement schedules, contrasting with the stabilizing effects of paroxetine. In the marble-burying test, kisspeptin-10 increased compulsive behavior compared to paroxetine, underscoring its modulatory role in compulsivity. These effects likely reflect kisspeptin-10’s interaction with dopaminergic and serotonergic systems, extending its influence beyond reproductive functions.

Conclusion: Kisspeptin-10 dose 1 mg/kg significantly modulates impulsive and compulsive behaviors, as well as reinforcing mechanisms, highlighting its potential as a therapeutic target for conditions characterized by dysregulated decision-making and compulsivity.